Defective pro-SFTPC causes SMDP2 and RDS

Stable Identifier
Homo sapiens
Defective pro-SFTPC causes pulmonary surfactant metabolism dysfunction 2 (SMDP2) and respiratory distress syndrome (RDS)
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Pulmonary surfactant-associated protein C (SFTPC), amongst other roles, is a component of surfactant, a surface-active film that helps reduce surface tension in alveoli. Defects in the SFTPC gene result in protein misfolding, misrouting and/or misprocessing resulting in accumulation of partially-processed, inactive pro-SFTPC in alveoli causing cell toxicity. Defects in SFTPC can cause pulmonary surfactant metabolism dysfunction 2 (SMDP2; MIM:610913), a rare lung disorder due to impaired surfactant homeostasis characterised by alveoli filling with floccular material. Cellular responses to the misfolded pro-SFTPC products include ER stress, the activation of reactive oxygen species and autophagy. Excessive lipoprotein accumulation in the alveoli results in a form of respiratory distress syndrome in premature infants (RDS; MIM:267450) (Thomas et al. 2002, Mulugeta et al. 2005, Thurm et al. 2013, Whitsett et al. 2015).
Literature References
PubMed ID Title Journal Year
23701443 SFTPC mutations cause SP-C degradation and aggregate formation without increasing ER stress

Zarbock, R, Griese, M, Thurm, T, Kern, S, Kaltenborn, E

Eur. J. Clin. Invest. 2013
11991887 Heterozygosity for a surfactant protein C gene mutation associated with usual interstitial pneumonitis and cellular nonspecific interstitial pneumonitis in one kindred

Stahlman, M, Johnson, J, Schwartz, DA, Phillips, J, Marney, A, Prince, M, Gaddipati, R, Markin, C, Thomas, AQ, Speer, M, Loyd, JE, Haines, J, Roberts, R, Lane, K

Am. J. Respir. Crit. Care Med. 2002
25621661 Diseases of pulmonary surfactant homeostasis

Whitsett, JA, Weaver, TE, Wert, SE

Annu Rev Pathol 2015
15778495 A surfactant protein C precursor protein BRICHOS domain mutation causes endoplasmic reticulum stress, proteasome dysfunction, and caspase 3 activation

Muniswamy, M, Mulugeta, S, Russo, SJ, Nguyen, V, Beers, MF

Am. J. Respir. Cell Mol. Biol. 2005
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
interstitial lung disease DOID:3082 ILD
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