ABCA3

ATP binding cassette subfamily A member 3, the group of ATP binding cassette subfamily A

Basic information

Region (hg38): 16:2275880-2340746

Previous symbols: [ "ABC3" ]

Links

ENSG00000167972 ∙ NCBI:21 ∙ OMIM:601615 ∙ HGNC:33 ∙ Uniprot:Q99758 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• interstitial lung disease due to ABCA3 deficiency (Strong), mode of inheritance: AR
• interstitial lung disease due to ABCA3 deficiency (Supportive), mode of inheritance: AR
• interstitial lung disease due to ABCA3 deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Surfactant metabolism dysfunction, pulmonary, 3	AR	Pulmonary	Individuals may present in infancy with severe respiratory insufficiency (a presentation in early childhood ascribed to a heterozygous variant has also beeen described), and diagnosis has important therapeutic implications, as BMT can be effective; Lung transplant may be beneficial in some individuals	Pulmonary	15044640; 15976379; 15819986; 15985750; 17719949; 22337229; 22304854; 23166334

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ABCA3 gene.

• not provided (494 variants)
• Hereditary pulmonary alveolar proteinosis (293 variants)
• Interstitial lung disease due to ABCA3 deficiency (278 variants)
• Inborn genetic diseases (52 variants)
• not specified (40 variants)
• Interstitial lung disease 2 (15 variants)
• ABCA3-related condition (10 variants)
• See cases (4 variants)
• Pulmonary Surfactant Metabolism Dysfunction, Recessive (4 variants)
• Primary interstitial lung disease specific to childhood due to pulmonary surfactant protein anomalies (2 variants)
• Pulmonary arterial hypertension;Respiratory distress;Neonatal respiratory distress (2 variants)
• Pulmonary lymphangiectasia (1 variants)
• Primary interstitial lung disease specific to childhood due to pulmonary surfactant protein anomalies;Diffuse interstitial pulmonary fibrosis (1 variants)
• Bullous lung disease (1 variants)
• Diffuse interstitial pulmonary fibrosis;Primary interstitial lung disease specific to childhood due to pulmonary surfactant protein anomalies (1 variants)
• Chromosome 22q11.2 deletion syndrome, distal (1 variants)
• Respiratory failure (1 variants)
• Pulmonary arterial hypertension;Respiratory insufficiency;Pulmonary valve insufficiency (1 variants)
• Neonatal acute respiratory distress due to SP-B deficiency (1 variants)
• Abnormal pulmonary interstitial morphology (1 variants)
• Disorder of lung (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ABCA3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	11	181	5	198
missense	7	17	273	13	1	311
nonsense	17		1			18
start loss						0
frameshift	16	3	1			20
inframe indel		1	3			4
splice donor/acceptor (+/-2bp)	2	7				9
splice region			12	22	4	38
non coding	1		53	85	62	201
Total	43	29	342	279	68

Highest pathogenic variant AF is 0.0000394

Variants in ABCA3

This is a list of pathogenic ClinVar variants found in the ABCA3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-2275936-G-T		Interstitial lung disease due to ABCA3 deficiency	Uncertain significance (Jan 13, 2018)
16-2275982-G-A		Interstitial lung disease due to ABCA3 deficiency	Uncertain significance (Jan 12, 2018)
16-2275985-C-T		Interstitial lung disease due to ABCA3 deficiency	Uncertain significance (Jan 13, 2018)
16-2276049-T-C		Interstitial lung disease due to ABCA3 deficiency	Uncertain significance (Jan 13, 2018)
16-2276053-G-A		Interstitial lung disease due to ABCA3 deficiency	Uncertain significance (Jan 13, 2018)
16-2276227-G-A		Interstitial lung disease due to ABCA3 deficiency	Uncertain significance (Mar 23, 2018)
16-2276241-G-A		Interstitial lung disease due to ABCA3 deficiency	Uncertain significance (Jan 13, 2018)
16-2276268-G-A		Interstitial lung disease due to ABCA3 deficiency	Uncertain significance (Jan 12, 2018)
16-2276295-G-A		Interstitial lung disease due to ABCA3 deficiency	Uncertain significance (Jan 13, 2018)
16-2276362-C-A		Interstitial lung disease due to ABCA3 deficiency	Benign (Jan 13, 2018)
16-2276385-C-T		Interstitial lung disease due to ABCA3 deficiency	Uncertain significance (Jan 13, 2018)
16-2276396-C-T		Interstitial lung disease due to ABCA3 deficiency	Uncertain significance (Jan 12, 2018)
16-2276406-C-T		Interstitial lung disease due to ABCA3 deficiency	Uncertain significance (Jan 13, 2018)
16-2276407-G-A		Interstitial lung disease due to ABCA3 deficiency	Uncertain significance (Jan 13, 2018)
16-2276471-A-C		Interstitial lung disease due to ABCA3 deficiency	Uncertain significance (Jan 13, 2018)
16-2276482-C-T		Interstitial lung disease due to ABCA3 deficiency	Uncertain significance (Jan 13, 2018)
16-2276519-C-T		Interstitial lung disease due to ABCA3 deficiency	Uncertain significance (Jan 13, 2018)
16-2276520-G-A		Interstitial lung disease due to ABCA3 deficiency	Uncertain significance (Jan 13, 2018)
16-2276578-A-G		Interstitial lung disease due to ABCA3 deficiency	Uncertain significance (Jan 12, 2018)
16-2276666-G-A		Interstitial lung disease due to ABCA3 deficiency	Uncertain significance (Mar 30, 2018)
16-2276673-C-T		Interstitial lung disease due to ABCA3 deficiency	Uncertain significance (Jan 13, 2018)
16-2276679-G-A		Hereditary pulmonary alveolar proteinosis	Uncertain significance (Oct 03, 2016)
16-2276679-G-GC			Uncertain significance (Aug 20, 2022)
16-2276680-C-T			Likely benign (Jul 06, 2023)
16-2276683-C-T			Likely benign (Sep 10, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ABCA3	protein_coding	protein_coding	ENST00000301732	30	64866

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.62e-8	1.00	125698	0	50	125748	0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.323	995	1.02e+3	0.972	0.0000732	11067
Missense in Polyphen		203	259.83	0.78129		3007
Synonymous	-2.75	542	466	1.16	0.0000380	3484
Loss of Function	5.02	26	72.0	0.361	0.00000356	812

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000664	0.000662
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000177	0.000176
Middle Eastern	0.000163	0.000163
South Asian	0.000131	0.000131
Other	0.000654	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays an important role in the formation of pulmonary surfactant, probably by transporting lipids such as cholesterol.
• Disease: DISEASE: Pulmonary surfactant metabolism dysfunction 3 (SMDP3) [MIM:610921]: A rare lung disorder due to impaired surfactant homeostasis. It is characterized by alveolar filling with floccular material that stains positive using the periodic acid- Schiff method and is derived from surfactant phospholipids and protein components. Excessive lipoproteins accumulation in the alveoli results in severe respiratory distress. {ECO:0000269|PubMed:15044640}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: ABC transporters - Homo sapiens (human);ABC transporters in lipid homeostasis;Surfactant metabolism;Metabolism of proteins;Transport of small molecules;ABC-family proteins mediated transport;Validated nuclear estrogen receptor alpha network (Consensus)

Recessive Scores

• pRec: 0.170

Intolerance Scores

• loftool: 0.0274
• rvis_EVS: -1.48
• rvis_percentile_EVS: 3.71

Haploinsufficiency Scores

• pHI: 0.134
• hipred: Y
• hipred_score: 0.663
• ghis: 0.488

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.737

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Abca3
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype

Gene ontology

• Biological process: lipid transport;response to drug;cellular protein metabolic process;response to glucocorticoid;transmembrane transport
• Cellular component: extracellular space;plasma membrane;membrane;integral component of membrane;intracellular membrane-bounded organelle;alveolar lamellar body;lamellar body membrane;alveolar lamellar body membrane
• Molecular function: transporter activity;lipid transporter activity;ATP binding;ATPase activity, coupled to transmembrane movement of substances