ABCA3

Chr 16

ATP binding cassette subfamily A member 3

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

NCBI Gene: 21 ENSG00000167972 UniProt: Q99758

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.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPulmonary surfactant metabolism dysfunction 3

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · interstitial lung disease due to ABCA3 deficiency · AR · ClinGen 2024

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.50

LOEUF

Multiple*

Mechanism· predicted

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GeneReview available — ABCA3

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

0.32Z-score

OE missense 0.97 (0.92–1.02)

995 obs / 1024.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.36 (0.26–0.50)

0≤0.351.4

Missense OE?0.97 (0.92–1.02)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 26 / 72.0Missense obs/exp: 995 / 1024.1Syn Z: -2.75

Background carrier burden — how many people carry a rare variant somewhere in ABCA3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 23

2,282 rare PASS variants

Rare truncating (LoF)

1 in 1,300

188 rare PASS variants

Rare synonymous (reference)

1 in 36

1,123 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ABCA3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 30	1 in 1,400
South Asian	~43k	1 in 18	1 in 870
Remaining (unassigned)	~30k	1 in 19	1 in 1,200
European (Finnish)	~27k	1 in 61	1 in 1,100
Admixed American	~22k	1 in 21	1 in 1,900
African / African American	~21k	1 in 21	1 in 1,700
East Asian	~20k	1 in 26	1 in 3,800
Ashkenazi Jewish	~13k	1 in 41	1 in 1,300
Middle Eastern	~2,884	1 in 19	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 30 coding exons well covered in gnomAD exomes and genomes.? see exons ↓