CSF2RB

Summary

CSF2RB (colony stimulating factor 2 receptor subunit beta, HGNC:2436) is a protein-coding gene on chromosome 22q12.3, encoding Cytokine receptor common subunit beta (P32927). Cell surface receptor that plays a role in immune response and controls the production and differentiation of hematopoietic progenitor cells into lineage-restricted cells.

The protein encoded by this gene is the common beta chain of the high affinity receptor for IL-3, IL-5 and CSF. Defects in this gene have been reported to be associated with protein alveolar proteinosis (PAP).

Source: NCBI Gene 1439 — RefSeq curated summary.

At a glance

• Gene–disease (curated): surfactant metabolism dysfunction, pulmonary, 5 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 16
• Clinical variants (ClinVar): 882 total — 1 pathogenic
• Phenotypes (HPO): 23
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_000395

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2436
Approved symbol	CSF2RB
Name	colony stimulating factor 2 receptor subunit beta
Location	22q12.3
Locus type	gene with protein product
Status	Approved
Aliases	IL5RB, CD131, betaGMR
Ensembl gene	ENSG00000100368
Ensembl biotype	protein_coding
OMIM	138981
Entrez	1439

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000403662, ENST00000406230, ENST00000421539, ENST00000910856, ENST00000910857

RefSeq mRNA: 2 — MANE Select: NM_000395 NM_000395, NM_001410827

CCDS: CCDS13936, CCDS93160

Canonical transcript exons

ENST00000403662 — 14 exons

Exon	Start	End
ENSE00000653699	36929402	36929559
ENSE00000653700	36929639	36929807
ENSE00000653701	36930375	36930510
ENSE00000653702	36930673	36930830
ENSE00000653703	36932765	36932904
ENSE00000653704	36933832	36933994
ENSE00000653707	36935630	36935687
ENSE00000653708	36936549	36936652
ENSE00000880095	36935351	36935441
ENSE00001547917	36922036	36922283
ENSE00001827597	36937377	36940439
ENSE00001920526	36913628	36913677
ENSE00003602454	36925987	36926177
ENSE00003651733	36923244	36923367

Expression profiles

Bgee: expression breadth ubiquitous, 230 present calls, max score 96.86.

FANTOM5 (CAGE): breadth broad, TPM avg 31.9862 / max 1566.2001, expressed in 678 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192077	31.0379	664
192076	0.4479	200
192080	0.2061	66
192081	0.1916	68
192079	0.0537	32
192078	0.0283	15
192082	0.0207	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	96.86	gold quality
periodontal ligament	UBERON:0008266	96.69	gold quality
decidua	UBERON:0002450	95.21	gold quality
vermiform appendix	UBERON:0001154	95.00	gold quality
epithelium of nasopharynx	UBERON:0001951	94.84	gold quality
mononuclear cell	CL:0000842	94.59	gold quality
monocyte	CL:0000576	94.57	gold quality
leukocyte	CL:0000738	94.56	gold quality
placenta	UBERON:0001987	94.22	gold quality
bone marrow	UBERON:0002371	93.57	gold quality
bone marrow cell	CL:0002092	93.06	gold quality
bone element	UBERON:0001474	91.20	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.19	gold quality
trabecular bone tissue	UBERON:0002483	90.59	gold quality
visceral pleura	UBERON:0002401	90.23	gold quality
granulocyte	CL:0000094	90.22	gold quality
lymph node	UBERON:0000029	90.12	gold quality
pleura	UBERON:0000977	89.28	gold quality
caecum	UBERON:0001153	88.72	gold quality
parietal pleura	UBERON:0002400	88.62	gold quality
endometrium epithelium	UBERON:0004811	86.79	gold quality
palpebral conjunctiva	UBERON:0001812	86.48	gold quality
spleen	UBERON:0002106	85.67	gold quality
tonsil	UBERON:0002372	84.32	gold quality
superficial temporal artery	UBERON:0001614	84.25	gold quality
frontal pole	UBERON:0002795	83.47	gold quality
paraflocculus	UBERON:0005351	83.19	gold quality
skin of hip	UBERON:0001554	83.17	gold quality
middle frontal gyrus	UBERON:0002702	82.64	gold quality
amniotic fluid	UBERON:0000173	82.31	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	1649.31
E-CURD-6	yes	367.10
E-HCAD-6	yes	59.14
E-MTAB-9067	yes	18.28
E-MTAB-6678	yes	17.42
E-CURD-112	yes	10.23
E-ANND-3	yes	5.89
E-CURD-88	yes	5.01

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RCOR1, SPI1

miRNA regulators (miRDB)

111 targeting CSF2RB, 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-6867-5P	100.00	82.21	3464
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 33)

• hGM-CSF activation of hGM/beta(c)with or w/o the hbeta(c) subunit, promoted primitive phenotype maintenance, indicating that the hGM Ralpha chain cytosolic domain is needed for differentiation mediated by the hGM Ralpha, beta(c) receptor complex. (PMID:12384414)
• soluble forms of the GM-CSF receptor alpha chain and beta chain were produced and a novel mechanism of receptor assembly was demonstrated (PMID:12393492)
• JAK2 activation mediates cross-talk between extracellular domain mutants of the beta-subunit of the GM-CSF receptor and EpoR (PMID:12488507)
• Interleukin-3 binding to the human betac receptor involves functional epitopes formed by domains 1 and 4 of different protein chains (PMID:15060062)
• A minor improvement in resolution has given a clearer indication of the position and stabilization of the key residues Tyr15, Phe79, Tyr347, His349, Ile350 and Tyr403 in the elbow region between domain 1 and domain 4 of the dimer-related molecule. (PMID:16754968)
• These results suggest that the JAK1-JH7-3 domains are required for interleukin-3 receptor common beta subunit interaction and abolish wild type JAK1 and JAK2-mediated signaling. (PMID:16767694)
• This study found that several markers (rs2072707, rs2284031 and rs909486)of csf2rb showed sex-specific and family history-dependent associations with schizophrenia. (PMID:17667962)
• The dynamic role of the common signaling subunit beta c is to prevent IL5alpha and GM-CSF ligand-receptor complexes from rapidly dissociating. (PMID:18294864)
• The interaction between intercellular adhesion molecule 1 (ICAM-1) and the GM-CSF receptor is essential for GM-CSF-induced eosinophil activation and survival. (PMID:18322230)
• IL-5-induced effects on betac assembly in the presence of nontagged IL-5Ralpha provide direct evidence that IL-5 can cause higher order rearrangements of betac homo-oligomers (PMID:18326494)
• Ligand-binding and receptor activation are not critically dependent on individual N-glycosylation sites within the IL-3- and IL-5-receptor common beta-subunit. (PMID:18374598)
• Data show that Deletion of the Ig-like domain of GM-CSFRalpha abolished direct GM-CSF binding and decreased growth signalling in the presence of hbetac. (PMID:20078425)
• Two different modes of beta c binding are utilized in the presence of the hIL-3R alpha isoforms. (PMID:20472554)
• the domain 1 D-E loop disulfide of hbetac and beta(IL-3) have roles in maintaining the precise positions of ligand-binding residues necessary for normal high affinity binding and signaling (PMID:20516062)
• Granulocyte/macrophage colony-stimulating factor causes a paradoxical increase in the BH3-only pro-apoptotic protein Bim in human neutrophils (PMID:20705940)
• The beta1 integrin-interacting domain in the extracellular domain of IL-3Rbeta was identified. A fragment of a protein corresponding to domain 4 of IL-3Rbeta prevented IL-3-mediated arterial morphogenesis and endothelial cell migration. (PMID:20802515)
• Over expression of IL-3Ralpha and truncated mutation of hbetac may be involved in proliferation and differentiation block in NB4 cells. (PMID:21176354)
• Hereditary pulmonary alveolar proteinosis caused by recessive CSF2RB mutations [case report] (PMID:21205713)
• the up-regulation of IL-3Rbeta expression may contribute to the maintenance of proliferation rather than cell differentiation. (PMID:21207215)
• The results of the study support CSF2RB as a risk factor common to both schizophrenia and major depression in the Chinese Han population. (PMID:21247258)
• JAK kinase binding to betac requires the presence of three critical betac lysine residues, and this binding event is essential for receptor ubiquitination, endocytosis, and signaling. (PMID:21965659)
• This study reveals a novel functional role of clathrin-coated structure in GMR signaling and the oncogenesis of JAK2V617F. (PMID:22935703)
• These data suggest that expression of GM-CSF and its receptor subunits by colon tumors may be a useful marker for prognosis (PMID:23108143)
• VitD-mediated stimulation of GC anti-inflammatory affects human monocytes in a process involving GM-CSF and MED14 (PMID:23572530)
• Exome sequencing identified candidate variants, including a missense mutation in DUOX2 that impaired its function and a frameshift mutation in CSF2RB that was associated with Crohn’s Disease in an independent cohort of Ashkenazi Jewish individuals. (PMID:27373512)
• In a genetic analysis of Ashkenazi Jewish individuals, we associated Crohn’s Disease with a frameshift mutation in CSF2RB. Intestinal monocytes from carriers of this mutation had reduced responses to granulocyte-macrophage colony-stimulating factor, providing an additional mechanism for alterations to the innate immune response in individuals with Crohn’s Disease. (PMID:27377463)
• SYK mediates the actions of EPO and GM-CSF and coordinates with TGF-beta in erythropoiesis. (PMID:28131718)
• This study provides a platform for studying the in vivo effect of Flt3-L and GM-CSF on human DCs and regulatory T cells. (PMID:29892279)
• Missense mutations in CSF2RB gene is associated with Pediatric Crohn’s Disease. (PMID:30124884)
• Genetic determinants of risk in autoimmune pulmonary alveolar proteinosis. (PMID:33589587)
• The Truncated Splice Variant of the Granulocyte-Macrophage-Colony-Stimulating Factor Receptor beta- Chain in Peripheral Blood Serves as Severity Biomarker of Respiratory Failure in Newborns. (PMID:33784678)
• Discovery of a novel potentially transforming somatic mutation in CSF2RB gene in breast cancer. (PMID:34729943)
• The IL-3, IL-5, and GM-CSF common receptor beta chain mediates oncogenic activity of FLT3-ITD-positive AML. (PMID:34750506)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Csf2rb	ENSMUSG00000071713
mus_musculus	Csf2rb2	ENSMUSG00000071714
rattus_norvegicus	Csf2rb	ENSRNOG00000000187

Paralogs (7): IL4R (ENSG00000077238), IL2RB (ENSG00000100385), IL21R (ENSG00000103522), MPL (ENSG00000117400), IL9R (ENSG00000124334), IL7R (ENSG00000168685), EPOR (ENSG00000187266)

Protein

Protein identifiers

Cytokine receptor common subunit beta — P32927 (reviewed: P32927)

Alternative names: CDw131, GM-CSF/IL-3/IL-5 receptor common beta subunit

All UniProt accessions (2): P32927, B0QY07

UniProt curated annotations — full annotation on UniProt →

Function. Cell surface receptor that plays a role in immune response and controls the production and differentiation of hematopoietic progenitor cells into lineage-restricted cells. Acts by forming an heterodimeric receptor through interaction with different partners such as IL3RA, IL5RA or CSF2RA. In turn, participates in various signaling pathways including interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor/CSF2 pathways. In unstimulated conditions, interacts constitutively with JAK1 and ligand binding leads to JAK1 stimulation and subsequent activation of the JAK-STAT pathway.

Subunit / interactions. Heterodimer of an alpha and a beta subunit. The beta subunit is common to the IL3, IL5 and GM-CSF receptors. The signaling GM-CSF receptor complex is a dodecamer of two head-to-head hexamers of two alpha, two beta, and two ligand subunits. Interacts with TMEM102; this interaction occurs preferentially in the absence of CSF2. Interacts with FCER1G; this interaction is direct. Interacts with LYN. Interacts with JAK1.

Subcellular location. Membrane.

Post-translational modifications. May be phosphorylated by LYN.

Disease relevance. Pulmonary surfactant metabolism dysfunction 5 (SMDP5) [MIM:614370] A rare lung disorder due to impaired surfactant homeostasis. It is characterized by alveolar filling with floccular material that stains positive using the periodic acid-Schiff method and is derived from surfactant phospholipids and protein components. Excessive lipoproteins accumulation in the alveoli results in severe respiratory distress. 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.

Similarity. Belongs to the type I cytokine receptor family. Type 4 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P32927-1	1	yes
P32927-2	2

RefSeq proteins (2): NP_000386, NP_001397756 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003531	Hempt_rcpt_S_F1_CS	Conserved_site
IPR003961	FN3_dom	Domain
IPR011365	IL3_rcpt_beta	Family
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR048668	IL3RB_N	Domain

Pfam: PF21460

UniProt features (79 total): strand 36, helix 9, disulfide bond 5, sequence variant 5, region of interest 4, compositionally biased region 3, glycosylation site 3, turn 3, short sequence motif 2, topological domain 2, domain 2, signal peptide 1, chain 1, modified residue 1, splice variant 1, transmembrane region 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
2GYS	X-RAY DIFFRACTION	2.7
1EGJ	X-RAY DIFFRACTION	2.8
1GH7	X-RAY DIFFRACTION	3
4NKQ	X-RAY DIFFRACTION	3.3
6NMY	X-RAY DIFFRACTION	3.3
8TLD	ELECTRON MICROSCOPY	3.6
5DWU	X-RAY DIFFRACTION	3.97
1C8P	SOLUTION NMR
2NA8	SOLUTION NMR
2NA9	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P32927-F1	65.50	0.38

Antibody-complex structures (SAbDab): 2 — 1EGJ, 5DWU

Functional residue map

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

Post-translational modifications (1): 766

Disulfide bonds (5): 35–45, 75–96, 86–91, 250–260, 289–306

Glycosylation sites (3): 58, 191, 346

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-512988	Interleukin-3, Interleukin-5 and GM-CSF signaling
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-5683826	Surfactant metabolism
R-HSA-5688849	Defective CSF2RB causes SMDP5
R-HSA-5688890	Defective CSF2RA causes SMDP4
R-HSA-912526	Interleukin receptor SHC signaling

MSigDB gene sets: 359 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, REACTOME_INTERLEUKIN_2_FAMILY_SIGNALING, CREL_01, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, MCLACHLAN_DENTAL_CARIES_UP, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, MODULE_255, GOBP_RESPONSE_TO_PEPTIDE, STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN, MODULE_45, MODULE_64, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, MODULE_317

GO Biological Process (12): signal transduction (GO:0007165), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), respiratory gaseous exchange by respiratory system (GO:0007585), immunoglobulin mediated immune response (GO:0016064), response to lipopolysaccharide (GO:0032496), cellular response to interleukin-3 (GO:0036016), interleukin-5-mediated signaling pathway (GO:0038043), interleukin-3-mediated signaling pathway (GO:0038156), granulocyte-macrophage colony-stimulating factor signaling pathway (GO:0038157), positive regulation of leukocyte proliferation (GO:0070665), cell surface receptor signaling pathway (GO:0007166), cytokine-mediated signaling pathway (GO:0019221)

GO Molecular Function (6): cytokine receptor activity (GO:0004896), coreceptor activity (GO:0015026), signaling receptor activity (GO:0038023), interleukin-3 receptor activity (GO:0004912), interleukin-5 receptor activity (GO:0004914), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), granulocyte macrophage colony-stimulating factor receptor complex (GO:0030526), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Diseases associated with surfactant metabolism	2
Signaling by Interleukins	1
MAPK1/MAPK3 signaling	1
Metabolism of proteins	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
cytokine-mediated signaling pathway	4
cellular response to cytokine stimulus	2
cytokine receptor activity	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell surface receptor signaling pathway via STAT	1
multicellular organismal process	1
B cell mediated immunity	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
response to interleukin-3	1
positive regulation of cell population proliferation	1
leukocyte proliferation	1
regulation of leukocyte proliferation	1
signal transduction	1
cell surface receptor signaling pathway	1
transmembrane signaling receptor activity	1
cytokine binding	1
immune receptor activity	1
signaling receptor activity	1
molecular transducer activity	1
interleukin-3 binding	1
cellular response to interleukin-3	1
interleukin-3-mediated signaling pathway	1
interleukin-5 binding	1
interleukin-5-mediated signaling pathway	1
binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
plasma membrane signaling receptor complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1875 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CSF2RB	CSF2RA	P15509	996
CSF2RB	CSF2	P04141	995
CSF2RB	EPOR	P19235	985
CSF2RB	IL3	P08700	984
CSF2RB	IL5	P05113	953
CSF2RB	IL3RA	P26951	942
CSF2RB	IL5RA	Q01344	932
CSF2RB	EPO	P01588	721
CSF2RB	CSF3R	Q99062	651
CSF2RB	JAK2	O60674	646
CSF2RB	ITGAM	P11215	608
CSF2RB	STAT5A	P42229	593
CSF2RB	CSF1R	P07333	580
CSF2RB	CSF1	P09603	562
CSF2RB	IL6R	P08887	552

IntAct

34 interactions, top by confidence:

A	B	Type	Score
IL3	IL3RA	psi-mi:“MI:0915”(physical association)	0.610
IL5RA	CSF2RB	psi-mi:“MI:0915”(physical association)	0.590
CSF2RB	IL3	psi-mi:“MI:0915”(physical association)	0.590
CSF2RB	JAK2	psi-mi:“MI:0915”(physical association)	0.560
CSF2RB	JAK2	psi-mi:“MI:0914”(association)	0.560
ITGB1	CSF2RB	psi-mi:“MI:0915”(physical association)	0.540
CSF2RB	ITGB1	psi-mi:“MI:0915”(physical association)	0.540
ITGB1	CSF2RB	psi-mi:“MI:0407”(direct interaction)	0.540
SHC1	CSF2RB	psi-mi:“MI:0914”(association)	0.530
PTPN11	CSF2RB	psi-mi:“MI:0914”(association)	0.530
CSF2	CSF2RB	psi-mi:“MI:0915”(physical association)	0.520
CSF2RB	IL5	psi-mi:“MI:0915”(physical association)	0.520
PTPN6	CSF2RB	psi-mi:“MI:0914”(association)	0.470
CSF2RB	PIK3R1	psi-mi:“MI:0914”(association)	0.460
JAK1	CSF2RB	psi-mi:“MI:0915”(physical association)	0.400
CSF2	CSF2RA	psi-mi:“MI:0915”(physical association)	0.400
IL3RA	CSF2RB	psi-mi:“MI:0915”(physical association)	0.400
KRAS	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350

BioGRID (39): CSF2RB (Affinity Capture-Western), KDR (Affinity Capture-Western), CSF2RB (Affinity Capture-MS), PTPN11 (Affinity Capture-Western), CSF2RB (Affinity Capture-Western), PTPN11 (Affinity Capture-Western), SHC1 (Affinity Capture-Western), STAT3 (Affinity Capture-Western), JAK1 (Affinity Capture-Western), PTPN11 (Affinity Capture-Western), PTPN6 (Affinity Capture-Western), PTPN6 (Reconstituted Complex), PTPN11 (Reconstituted Complex), CSF2RB (Co-crystal Structure), CSF2RB (Reconstituted Complex)

ESM2 similar proteins: A0A1B0GV85, A2APT9, A2BDP1, A2IDD5, A5PJC7, B0BN44, E9PGG2, O14836, P0C1G7, P0C8S2, P20333, P32927, P97764, Q01114, Q2KI80, Q3TS39, Q3TYX8, Q3URD2, Q4KLY2, Q4V9L6, Q5F267, Q5FVJ4, Q5JXC2, Q5R866, Q5RA50, Q5SW24, Q5T7N3, Q5VTJ3, Q6PAL1, Q6PJ61, Q6ZNE9, Q7TN08, Q80VJ8, Q86V42, Q8BG80, Q8BRJ3, Q8BX43, Q8CAE9, Q8N112, Q8NBI3

Diamond homologs: P14784, P16297, P26896, P26955, P32927, Q38J84, Q38J85, P26954

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
PTPN6	down-regulates	CSF2RB	dephosphorylation
CSF2RB	“form complex”	CSF2RA/CSF2RB	binding
BCR-ABL	“up-regulates activity”	CSF2RB	phosphorylation
PTPN11	up-regulates	CSF2RB	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 17 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Interleukin receptor SHC signaling	11	280.4×	2e-24
Interleukin-3, Interleukin-5 and GM-CSF signaling	13	257.7×	6e-29
Signaling by CSF3 (G-CSF)	5	178.4×	4e-09
RAF/MAP kinase cascade	11	42.0×	9e-15
Interleukin-4 and Interleukin-13 signaling	5	32.1×	1e-05
Signaling by Interleukins	6	24.1×	4e-06
SARS-CoV Infections	5	17.3×	1e-04
Cytokine Signaling in Immune system	6	15.3×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
cytokine-mediated signaling pathway	10	81.7×	2e-15
immune response	5	14.7×	5e-04

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	484
Likely benign	312
Benign	58

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
29744	NM_000395.3(CSF2RB):c.631del (p.Arg211fs)	Pathogenic

SpliceAI

2282 predictions. Top by Δscore:

Variant	Effect	Δscore
22:36913675:GAG:G	donor_gain	1.0000
22:36913676:AGG:A	donor_loss	1.0000
22:36913677:GGTA:G	donor_loss	1.0000
22:36923365:TGA:T	donor_gain	1.0000
22:36923366:GA:G	donor_gain	1.0000
22:36923366:GAG:G	donor_gain	1.0000
22:36923368:G:GG	donor_gain	1.0000
22:36932759:CTCCA:C	acceptor_loss	1.0000
22:36932760:TCCAG:T	acceptor_loss	1.0000
22:36932761:CCA:C	acceptor_loss	1.0000
22:36932762:CAGTC:C	acceptor_loss	1.0000
22:36932763:A:AG	acceptor_gain	1.0000
22:36932763:A:C	acceptor_loss	1.0000
22:36932764:G:A	acceptor_loss	1.0000
22:36932764:G:GA	acceptor_gain	1.0000
22:36932764:GTCC:G	acceptor_gain	1.0000
22:36932764:GTCCA:G	acceptor_gain	1.0000
22:36932884:A:T	donor_gain	1.0000
22:36932902:AAGG:A	donor_loss	1.0000
22:36932903:AGG:A	donor_loss	1.0000
22:36932904:GGTGA:G	donor_loss	1.0000
22:36935338:C:A	acceptor_gain	1.0000
22:36935339:G:A	acceptor_gain	1.0000
22:36935342:T:A	acceptor_gain	1.0000
22:36935345:T:A	acceptor_gain	1.0000
22:36935617:T:TA	acceptor_gain	1.0000
22:36935628:A:AG	acceptor_gain	1.0000
22:36935629:G:GG	acceptor_gain	1.0000
22:36935686:AGGT:A	donor_loss	1.0000
22:36935687:GGT:G	donor_loss	1.0000

AlphaMissense

5815 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:36923308:G:C	W47C	0.998
22:36923308:G:T	W47C	0.998
22:36930442:G:C	W262C	0.998
22:36930442:G:T	W262C	0.998
22:36932824:T:A	W358R	0.996
22:36932824:T:C	W358R	0.996
22:36932826:G:C	W358C	0.996
22:36932826:G:T	W358C	0.996
22:36933961:T:A	W428R	0.996
22:36933961:T:C	W428R	0.996
22:36933963:G:C	W428C	0.995
22:36933963:G:T	W428C	0.995
22:36933981:G:C	W434C	0.994
22:36933981:G:T	W434C	0.994
22:36930440:T:A	W262R	0.993
22:36930440:T:C	W262R	0.993
22:36932866:T:C	F372L	0.993
22:36932868:T:A	F372L	0.993
22:36932868:T:G	F372L	0.993
22:36933955:A:C	S426R	0.992
22:36933957:C:A	S426R	0.992
22:36933957:C:G	S426R	0.992
22:36933964:A:C	S429R	0.992
22:36933966:T:A	S429R	0.992
22:36933966:T:G	S429R	0.992
22:36933979:T:A	W434R	0.992
22:36933979:T:C	W434R	0.992
22:36929776:G:C	W229C	0.991
22:36929776:G:T	W229C	0.991
22:36923270:T:A	C35S	0.990

dbSNP variants (sampled 300 via entrez): RS1000005478 (22:36913484 A>G), RS1000101933 (22:36926847 C>A), RS1000284692 (22:36924095 G>A), RS1000593123 (22:36934030 G>A,C), RS1000705246 (22:36938902 C>A,T), RS1000814023 (22:36917513 C>G,T), RS1000901690 (22:36928523 C>G,T), RS1001091267 (22:36911939 A>T), RS1001107217 (22:36928131 A>T), RS1001225707 (22:36931715 T>C), RS1001255355 (22:36931342 A>C,G), RS1001258006 (22:36917085 C>T), RS1001289082 (22:36916843 A>T), RS1001292804 (22:36931076 G>T), RS1001458429 (22:36936799 C>G)

Disease associations

OMIM: gene MIM:138981 | disease phenotypes: MIM:614370

GenCC curated gene-disease

Disease	Classification	Inheritance
surfactant metabolism dysfunction, pulmonary, 5	Moderate	Autosomal recessive
hereditary pulmonary alveolar proteinosis	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
surfactant metabolism dysfunction, pulmonary, 5	Definitive	AR

Mondo (2): surfactant metabolism dysfunction, pulmonary, 5 (MONDO:0013712), hereditary pulmonary alveolar proteinosis (MONDO:0012580)

Orphanet (1): Hereditary pulmonary alveolar proteinosis (Orphanet:264675)

HPO phenotypes

23 total (23 of 23 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001531	Failure to thrive in infancy
HP:0001649	Tachycardia
HP:0002091	Restrictive ventilatory defect
HP:0002093	Respiratory insufficiency
HP:0002094	Dyspnea
HP:0002098	Respiratory distress
HP:0002789	Tachypnea
HP:0002875	Exertional dyspnea
HP:0003651	Foam cells
HP:0004887	Respiratory failure requiring assisted ventilation
HP:0006517	Intraalveolar phospholipid accumulation
HP:0010876	Abnormal circulating protein concentration
HP:0011949	Acute infectious pneumonia
HP:0012418	Hypoxemia
HP:0012735	Cough
HP:0020050	Anti-granulocyte-macrophage colony stimulating factor antibody positivity
HP:0025179	Ground-glass opacification
HP:0025391	Crazy paving pattern
HP:0030057	Autoimmune antibody positivity
HP:0030830	Crackles
HP:0030879	Interlobular septal thickening
HP:0031029	Elevated circulating CEA concentration

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST003602_5	Inflammatory bowel disease	8.000000e-07
GCST004861_4	Itch intensity from mosquito bite	2.000000e-22
GCST004862_108	Itch intensity from mosquito bite adjusted by bite size	6.000000e-09
GCST004862_196	Itch intensity from mosquito bite adjusted by bite size	5.000000e-07
GCST004863_32	Mosquito bite size	4.000000e-22
GCST004864_6	Perceived unattractiveness to mosquitoes	2.000000e-06
GCST004865_4	Itch intensity from mosquito bite adjusted by bite size	3.000000e-07
GCST005531_73	Multiple sclerosis	1.000000e-06
GCST006585_1496	Blood protein levels	1.000000e-100
GCST007123_4	Multiple sclerosis and LDL levels (pleiotropy)	9.000000e-06
GCST009597_156	Multiple sclerosis	5.000000e-11
GCST012490_368	Femur bone mineral density x serum urate levels interaction	3.000000e-12
GCST90002381_444	Eosinophil count	2.000000e-14
GCST90002381_445	Eosinophil count	6.000000e-20
GCST90002382_506	Eosinophil percentage of white cells	4.000000e-15
GCST90002382_507	Eosinophil percentage of white cells	9.000000e-20

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0008380	perceived unattractiveness to mosquitos measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004531	urate measurement
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535832	Pulmonary alveolar proteinosis, congenital (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2364169 (PROTEIN COMPLEX), CHEMBL4804252 (PROTEIN COMPLEX)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — IL-3 receptor family

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases expression	2
TL8-506	increases expression, affects cotreatment	1
triphenyl phosphate	affects expression	1
terbufos	increases methylation	1
benzo(e)pyrene	decreases methylation, increases methylation	1
nickel sulfate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Decitabine	decreases reaction, decreases expression	1
Arsenic Trioxide	increases expression	1
Benzene	increases expression	1
Benzo(a)pyrene	increases methylation	1
Demecolcine	increases expression	1
Diethylhexyl Phthalate	increases expression	1
Fonofos	increases methylation	1
Flavonoids	increases expression	1
Formaldehyde	increases expression	1
Methapyrilene	decreases methylation, increases methylation	1
Naled	affects expression	1
Nickel	increases expression	1
Parathion	increases methylation	1
Plant Extracts	increases expression	1
Smoke	decreases expression, decreases reaction	1
Sodium Dodecyl Sulfate	increases expression	1
Sodium Glutamate	affects cotreatment, affects expression	1
Tretinoin	increases expression	1
Cyclosporine	increases methylation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01511068	PHASE2	COMPLETED	Inhaled Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in Hereditary Pulmonary Alveolar Proteinosis (PAP)
NCT05761899	PHASE1/PHASE2	RECRUITING	Safety and Efficacy of PMT Therapy of hPAP