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) is thought to play a role in the formation of pulmonary surfactant by transporting lipids such as cholesterol into lamellar bodies (LBs) in alveolar type II cells. In LBs, surfactant proteins and lipids are assembled into bilayer membranes that are secreted via ABCA3 into the alveolar airspace, where they form a surface film at the air–liquid interface. Defects in ABCA3 can cause pulmonary surfactant metabolism dysfunction 3 (SMDP3; MIM:610921), a usually fatal pulmonary disease in newborns, characterised structurally by the absence of normal LBs and the presence of electron-dense inclusions within small vesicular structures. Loss of secretion of lipid pulmonary surfactants causes excessive lipoprotein accumulation in the alveoli resulting in severe respiratory distress. Mutations causing SMDP3 include W1142*, L101P, L1553P, L326P, D253H and T1173R (Shulenin et al. 2004, Kunig et al. 2007, Flamein et al. 2012).

Literature References
PubMed ID Title Journal Year
17719949 ABCA3 deficiency presenting as persistent pulmonary hypertension of the newborn

Kunig, AM, Nogee, LM, Parker, TA, Kinsella, JP, Abman, SH

J. Pediatr. 2007
22068586 Molecular and cellular characteristics of ABCA3 mutations associated with diffuse parenchymal lung diseases in children

Pernelle, J, Brémont, F, Nogee, LM, Maurice, M, Brouard, J, Amselem, S, de Blic, J, Jonard, L, Inagaki, N, Flamein, F, Marguet, C, Feldmann, D, Epaud, R, Clement, A, Dubus, JC, Muselet-Charlier, C, Riffault, L, Durand-Schneider, AM, Coulomb, A, Guillot, L, Rigourd, V

Hum. Mol. Genet. 2012
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
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