Defective CSF2RA does not bind SFTPs

Stable Identifier
Reaction [transition]
Homo sapiens
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Surfactant catabolism by alveolar macrophages plays a small but critical part in surfactant recycling and metabolism. Upon ligand binding, granulocyte-macrophage colony-stimulating factor receptor (GM-CSF), a heterodimer of alpha (CSF2RA) and beta (CSF2RB) subunits, initiates a signalling process that not only induces proliferation, differentiation and functional activation of hematopoietic cells but can also determine surfactant uptake into alveolar macrophages and its degradation via clathrin-coated vesicles. Defects in human CSF2RA can cause pulmonary surfactant metabolism dysfunction 4 (SMDP4; MIM:300770, aka congenital pulmonary alveolar proteinosis (PAP)), a rare lung disorder due to impaired surfactant homeostasis characterised by alveoli filling with floccular material. Excessive lipoprotein accumulation in the alveoli results in a form of respiratory distress syndrome in premature infants (RDS; MIM:267450). Suzuki et al. identified a G to A transition in exon 7 of the CSF2RA gene from 2 sisters with PAP resulting in a G174R substitution that altered one of 11 potential N-glycosylation sites in the CSF2RA protein. The affected sisters expressed only a truncated form of CSF2RA. Ligand binding and CSF2-dependent signalling were severely reduced, but not abolished (Suzuki et al. 2008).
Literature References
PubMed ID Title Journal Year
18955570 Familial pulmonary alveolar proteinosis caused by mutations in CSF2RA

Suzuki, T, Wood, RE, Rubin, BK, Grabowski, G, Smolarek, T, Nogee, LM, Dishop, MK, Whitsett, JA, Trapnell, BC, Carey, BC, Sakagami, T, Wert, SE, van der Loo, JC, Stevens, C, Zimmerman, SL

J. Exp. Med. 2008
Normal reaction
Functional status

Loss of function of CSF2RA G174R:CSF2RB [plasma membrane]

Name Identifier Synonyms
newborn respiratory distress syndrome DOID:12716 Neonatal respiratory Distress syndrome, hyaline membrane disease, HMD - Hyaline membrane disease, pulmonary hypoperfusion syndrome of newborn, respiratory distress syndrome of newborn, pulmonary hyaline membrane disease
pulmonary alveolar proteinosis DOID:12120
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