Defective ABCA3 does not transport PC, PG from ER membrane to lamellar body

Stable Identifier
Reaction [transition]
Homo sapiens
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ATP-binding cassette sub-family A member 3 (ABCA3) plays an important role in the formation of pulmonary surfactant, probably by transporting phospholipids such as phosphatidylcholine (PC) and phosphatidylglycerol (PG) from the ER membrane to lamellar bodies (LBs). PC and PG are the major phospholipid constituents of pulmonary surfactant. LBs are the surfactant storage organelles of type II epithelial cells from where phospholipids can be secreted together with surfactant proteins (SFTPs) into the alveolar airspace. Defects in ABCA3 can cause pulmonary surfactant metabolism dysfunction type 3 (SMDP3; MIM:610921), resulting in respiratory distress in newborns and interstitial lung disease (ILD) in children. Mutations in ABCA3 that affect its transport function include E292V, N568D, E690K and T1114M (Shulenin et al. 2004, Matsumara et al. 2006, 2008, Kaltenborn et al. 2012).
Literature References
PubMed ID Title Journal Year
18676873 Aberrant catalytic cycle and impaired lipid transport into intracellular vesicles in ABCA3 mutants associated with nonfatal pediatric interstitial lung disease

Ban, N, Matsumura, Y, Inagaki, N

Am. J. Physiol. Lung Cell Mol. Physiol. 2008
22434821 Respiratory syncytial virus potentiates ABCA3 mutation-induced loss of lung epithelial cell differentiation

Conzelmann, KK, Zarbock, R, Kern, S, Griese, M, Fragnet, L, Frixel, S, Kaltenborn, E

Hum. Mol. Genet. 2012
16959783 Characterization and classification of ATP-binding cassette transporter ABCA3 mutants in fatal surfactant deficiency

Ban, N, Matsumura, Y, Inagaki, N, Ueda, K

J. Biol. Chem. 2006
15044640 ABCA3 gene mutations in newborns with fatal surfactant deficiency

Wert, SE, Annilo, T, Whitsett, JA, Nogee, LM, Shulenin, S, Dean, M

N Engl J Med 2004
Catalyst Activity

lipid transporter activity of ABCA3 mutants [lamellar body membrane]

Normal reaction
Functional status

Loss of function of ABCA3 mutants [lamellar body 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
interstitial lung disease DOID:3082 ILD
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