ABCA3

Chr 16AR

ATP binding cassette subfamily A member 3

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

NCBI Gene: 21ENSG00000167972UniProt: Q99758

The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. The full transporter encoded by this gene may be involved in development of resistance to xenobiotics and engulfment during programmed cell death. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Surfactant metabolism dysfunction, pulmonary, 3MIM #610921
AR
UniProtPulmonary surfactant metabolism dysfunction 3
570
ClinVar variants
50
Pathogenic / LP
0.00
pLI score
3
Active trials
Clinical Summary— ABCA3
🧬
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.
📋
ClinVar Variants
50 Pathogenic / Likely Pathogenic· 215 VUS of 570 total submissions
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.50LOEUF
pLI 0.000
Z-score 5.02
OE 0.36 (0.26–0.50)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.32Z-score
OE missense 0.97 (0.92–1.02)
995 obs / 1024.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.36 (0.26–0.50)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.92–1.02)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.16
0≤1.21.6
LoF obs/exp: 26 / 72.0Missense obs/exp: 995 / 1024.1Syn Z: -2.75

ClinVar Variant Classifications

570 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic29
VUS215
Likely Benign299
Benign3
Conflicting3
21
Pathogenic
29
Likely Pathogenic
215
VUS
299
Likely Benign
3
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
16
0
21
Likely Pathogenic
14
9
6
0
29
VUS
0
204
10
1
215
Likely Benign
0
7
123
169
299
Benign
0
1
2
0
3
Conflicting
—3
Total19221157170570

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Surfactant metabolism dysfunction, pulmonary, 3

MIM #610921

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — ABCA3
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genotype-phenotype correlations for infants and children with ABCA3 deficiency.
Wambach JA et al.·Am J Respir Crit Care Med
2014
European protocols for the diagnosis and initial treatment of interstitial lung disease in children.
Bush A et al.·Thorax
2015Review
ABCA3 Deficiency-Variant-Specific Response to Hydroxychloroquine.
Yang X et al.·Int J Mol Sci
2023
Human pluripotent stem cell modeling of alveolar type 2 cell dysfunction caused by ABCA3 mutations.
Sun YL et al.·J Clin Invest
2024Functional
Structural Features of the ATP-Binding Cassette (ABC) Transporter ABCA3.
Paolini A et al.·Int J Mol Sci
2015Review
ABCA3, a key player in neonatal respiratory transition and genetic disorders of the surfactant system.
Peca D et al.·Biochem Soc Trans
2015Review
Genetic Disorders of Surfactant Metabolism.
Nevel RJ et al.·Neoreviews
2025Review
Interstitial lung diseases in children.
Nathan N et al.·Presse Med
2020Review
ABCA3-related interstitial lung disease beyond infancy.
Li Y et al.·Thorax
2023
Functional Genomics of ABCA3 Variants.
Wambach JA et al.·Am J Respir Cell Mol Biol
2020Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Genetic features of Japanese children with ABCA3 deficiency.
Takeda K et al.·Early Hum Dev
2026
Functional analysis of ABCA3 transporters in lipid metabolism regulation of the silkworm, Bombyx mori.
Liu Q et al.·Insect Biochem Mol Biol
2025Functional
Phenotype-Genotype Correlations in ABCA3 Patients-The RespiRare Cohort.
Fleury M et al.·Pediatr Pulmonol
2025🔓 Open AccessCohort
A comparative analysis of clinical phenotypes and outcomes in childhood interstitial lung disease due to surfactant dysfunction disorders: focusing on mutations in SFTPC, ABCA3, and NKX2-1 genes.
Tang X et al.·Ital J Pediatr
2025🔓 Open Access
Progressive respiratory failure in a term neonate with ABCA3 surfactant deficiency: Beyond the common causes of respiratory distress.
Beverstock AM et al.·J Neonatal Perinatal Med
2026🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Familial Pulmonary Fibrosis

GEN-FPF: Genetic Exploration of Familial Pulmonary Fibrosis

RECRUITING
NCT07251725Fondazione IRCCS Policlinico San Matteo di PaviaStarted 2025-09-17
Interstitial Lung Diseases of ChildhoodGenetic Testing

Genetic Causes and Clinical Features of Childhood Interstitial Lung Diseases in China

ACTIVE NOT RECRUITING
NCT03869515Children's Hospital of Fudan UniversityStarted 2019-03-25
No intervention
Idiopathic Interstitial Pneumopathy/Pneumopathy Interstitial DiffusePaediatric and Adult Patients

RaDiCo PID Cohort (RaDiCo-ILD Cohort in English)

RECRUITING
NCT04238871Institut National de la Santé Et de la Recherche Médicale, FranceStarted 2017-06-21

External Resources

Links to major genomics databases and tools