ABCA3

Chr 16AR

ATP binding cassette subfamily A member 3

Also known as: ABC-C, ABC3, EST111653, LBM180, SMDP3

The protein catalyzes ATP-dependent transport of phospholipids from the cytoplasm into lamellar bodies, participating in surfactant biogenesis and homeostasis in the lungs. Mutations cause surfactant metabolism dysfunction, pulmonary type 3, inherited in an autosomal recessive pattern. Disease results from loss of normal protein function leading to defective surfactant production and severe respiratory dysfunction.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismARLOEUF 0.501 OMIM phenotype
Clinical SummaryABCA3
🧬
Gene-Disease Validity (ClinGen)
interstitial lung disease due to ABCA3 deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.50LOEUF
pLI 0.000
Z-score 5.02
OE 0.36 (0.260.50)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.32Z-score
OE missense 0.97 (0.921.02)
995 obs / 1024.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.36 (0.260.50)
00.351.4
Missense OE0.97 (0.921.02)
00.61.4
Synonymous OE1.16
01.21.6
LoF obs/exp: 26 / 72.0Missense obs/exp: 995 / 1024.1Syn Z: -2.75
DN
0.7326th %ile
GOF
0.73top 25%
LOF
0.2092th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ABCA3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗