ABCA3 (ATP binding cassette subfamily A member 3)

Gene

• Entrez ID: 21
• Gene name: ATP binding cassette subfamily A member 3
• Gene symbol: ABCA3
• Synonyms: ABC-C, ABC3, EST111653, LBM180, SMDP3
• Chromosome: 16
• Chromosome location: 16p13.3
• Summary: 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]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs28936691	T>G	Pathogenic	Missense variant, coding sequence variant
rs45592239	G>A	Uncertain-significance, likely-benign, conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs45620539	G>A	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs121909181	C>T	Pathogenic	Coding sequence variant, stop gained
rs121909182	A>G	Pathogenic	Coding sequence variant, missense variant
rs121909183	A>G	Pathogenic	Coding sequence variant, missense variant
rs121909184	T>C	Pathogenic	Coding sequence variant, missense variant
rs121909185	A>C,G	Uncertain-significance, pathogenic	Coding sequence variant, missense variant
rs141621969	G>A,T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs143929832	G>A,C,T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Coding sequence variant, missense variant
rs149989682	T>A,C	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs201299260	G>A,C	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs754714105	C>T	Pathogenic	Missense variant, coding sequence variant
rs756855585	->A	Likely-pathogenic	Frameshift variant, coding sequence variant
rs773223403	T>C	Likely-pathogenic	Splice acceptor variant
rs775903641	TGTAG>-	Pathogenic	Coding sequence variant, frameshift variant
rs876657633	GCACCTT>TGG	Likely-pathogenic	Splice donor variant, intron variant, coding sequence variant
rs973835010	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1567335355	C>T	Pathogenic	Splice donor variant
rs1596842934	C>G	Likely-pathogenic	Splice acceptor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT016946	hsa-miR-335-5p	Microarray	18185580
MIRT040559	hsa-miR-92b-3p	CLASH	23622248
MIRT049276	hsa-miR-92a-3p	CLASH	23622248
MIRT050565	hsa-miR-20a-5p	CLASH	23622248
MIRT441309	hsa-miR-409-5p	HITS-CLIP	24374217

Transcription factors

Transcription factor	Regulation	Reference
SALL4	Activation	21526180;23432194
SALL4A	Activation	21526180

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005319	Function	Lipid transporter activity	IBA	21873635
GO:0005319	Function	Lipid transporter activity	TAS
GO:0005524	Function	ATP binding	IEA
GO:0005615	Component	Extracellular space	HDA	22664934
GO:0005886	Component	Plasma membrane	IDA	11718719, 23137377
GO:0006855	Process	Drug transmembrane transport	IMP	26903515
GO:0006869	Process	Lipid transport	IBA	21873635
GO:0008559	Function	ABC-type xenobiotic transporter activity	IMP	26903515
GO:0010875	Process	Positive regulation of cholesterol efflux	IMP	25817392
GO:0015914	Process	Phospholipid transport	IMP	28887056
GO:0016021	Component	Integral component of membrane	IEA
GO:0016887	Function	ATPase activity	IDA	16959783
GO:0030324	Process	Lung development	ISS
GO:0030659	Component	Cytoplasmic vesicle membrane	IDA	16959783, 17574245, 20863830
GO:0032464	Process	Positive regulation of protein homooligomerization	IDA	27352740
GO:0042493	Process	Response to drug	TAS	8706931
GO:0042626	Function	ATPase-coupled transmembrane transporter activity	IBA	21873635
GO:0042908	Process	Xenobiotic transport	IMP	26903515
GO:0043129	Process	Surfactant homeostasis	ISS
GO:0043231	Component	Intracellular membrane-bounded organelle	IBA	21873635
GO:0044267	Process	Cellular protein metabolic process	TAS
GO:0046470	Process	Phosphatidylcholine metabolic process	IMP	17574245, 28887056
GO:0046470	Process	Phosphatidylcholine metabolic process	ISS
GO:0046471	Process	Phosphatidylglycerol metabolic process	ISS
GO:0046618	Process	Drug export	IMP	26903515
GO:0046890	Process	Regulation of lipid biosynthetic process	IEA
GO:0051384	Process	Response to glucocorticoid	IEA
GO:0055085	Process	Transmembrane transport	TAS
GO:0055091	Process	Phospholipid homeostasis	IEA
GO:0070925	Process	Organelle assembly	ISS
GO:0097208	Component	Alveolar lamellar body	IDA	11718719
GO:0097232	Component	Lamellar body membrane	IDA	20863830
GO:0097232	Component	Lamellar body membrane	TAS
GO:0097233	Component	Alveolar lamellar body membrane	IDA	11940594, 16959783
GO:0120009	Process	Intermembrane lipid transfer	IEA
GO:0120019	Function	Phosphatidylcholine transfer activity	IMP	28887056
GO:0140345	Function	Phosphatidylcholine flippase activity	IMP	31473345
GO:0150172	Process	Regulation of phosphatidylcholine metabolic process	IMP	25817392, 31473345
GO:1902995	Process	Positive regulation of phospholipid efflux	IMP	31473345

Other IDs

• MIM: 601615
• HGNC: 33
• e!Ensembl: ENSG00000167972

Protein

• UniProt ID: Q99758
• Protein name: Phospholipid-transporting ATPase ABCA3 (EC 7.6.2.1) (ABC-C transporter) (ATP-binding cassette sub-family A member 3) (ATP-binding cassette transporter 3) (ATP-binding cassette 3) (Xenobiotic-transporting ATPase ABCA3) (EC 7.6.2.2) [Cleaved into: 150 Kda mature form]
• Protein function: Catalyzes the ATP-dependent transport of phospholipids such as phosphatidylcholine and phosphoglycerol from the cytoplasm into the lumen side of lamellar bodies, in turn participates in the lamellar bodies biogenesis and homeostasis of pulmonary surfactant (PubMed:16959783, PubMed:17574245, PubMed:28887056, PubMed:31473345, PubMed:27177387). Transports preferentially phosphatidylcholine containing short acyl chains (PubMed:27177387). In addition plays a role as an efflux transporter of miltefosine across macrophage membranes and free cholesterol (FC) through intralumenal vesicles by removing FC from the cell as a component of surfactant and protects cells from free cholesterol toxicity (PubMed:26903515, PubMed:25817392, PubMed:27177387).
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF12698	ABC2_membrane_3	23 → 469		Family
  PF00005	ABC_tran	549 → 693	ABC transporter	Domain
  PF12698	ABC2_membrane_3	923 → 1323		Family
  PF00005	ABC_tran	1399 → 1543	ABC transporter	Domain

• Sequence:

  MAVLRQLALLLWKNYTLQKRKVLVTVLELFLPLLFSGILIWLRLKIQSENVPNATIYPGQ
  SIQELPLFFTFPPPGDTWELAYIPSHSDAAKTVTETVRRALVINMRVRGFPSEKDFEDYI
  RYDNCSSSVLAAVVFEHPFNHSKEPLPLAVKYHLRFSYTRRNYMWTQTGSFFLKETEGWH
  TTSLFPLFPNPGPREPTSPDGGEPGYIREGFLAVQHAVDRAIMEYHADAATRQLFQRLTV
  TIKRFPYPPFIADPFLVAIQYQLPLLLLLSFTYTALTIARAVVQEKERRLKEYMRMMGLS
  SWLHWSAWFLLFFLFLLIAASFMTLLFCVKVKPNVAVLSRSDPSLVLAFLLCFAISTISF
  SFMVSTFFSKANMAAAFGGFLYFFTYIPYFFVAPRYNWMTLSQKLCSCLLSNVAMAMGAQ
  LIGKFEAKGMGIQWRDLLSPVNVDDDFCFGQVLGMLLLDSVLYGLVTWYMEAVFPGQFGV
  PQPWYFFIMPSYWCGKPRAVAGKEEEDSDPEKALRNEYFEAEPEDLVAGIKIKHLSKVFR
  VGNKDRAAVRDLNLNLYEGQITVLLGHNGAGKTTTLSMLTGLFPPTSGRAYISGYEISQD
  MVQIRKSLGLCPQHDILFDNLTVAEHLYFYAQLKGLSRQKCPEEVKQMLHIIGLEDKWNS
  RSRFLSGGMRRKLSIGIALIAGSKVLILDEPTSGMDAISRRAIWDLLQRQKSDRTIVLTT
  HFMDEADLLGDRIAIMAKGELQCCGSSLFLKQKYGAGYHMTLVKEPHCNPEDISQLVHHH
  VPNATLESSAGAELSFILPRESTHRFEGLFAKLEKKQKELGIASFGASITTMEEVFLRVG
  KLVDSSMDIQAIQLPALQYQHERRASDWAVDSNLCGAMDPSDGIGALIEEERTAVKLNTG
  LALHCQQFWAMFLKKAAYSWREWKMVAAQVLVPLTCVTLALLAINYSSELFDDPMLRLTL
  GEYGRTVVPFSVPGTSQLGQQLSEHLKDALQAEGQEPREVLGDLEEFLIFRASVEGGGFN
  ERCLVAASFRDVGERTVVNALFNNQAYHSPATALAVVDNLLFKLLCGPHASIVVSNFPQP
  RSALQAAKDQFNEGRKGFDIALNLLFAMAFLASTFSILAVSERAVQAKHVQFVSGVHVAS
  FWLSALLWDLISFLIPSLLLLVVFKAFDVRAFTRDGHMADTLLLLLLYGWAIIPLMYLMN
  FFFLGAATAYTRLTIFNILSGIATFLMVTIMRIPAVKLEELSKTLDHVFLVLPNHCLGMA
  VSSFYENYETRRYCTSSEVAAHYCKKYNIQYQENFYAWSAPGVGRFVASMAASGCAYLIL
  LFLIETNLLQRLRGILCALRRRRTLTELYTRMPVLPEDQDVADERTRILAPSPDSLLHTP
  LIIKELSKVYEQRVPLLAVDRLSLAVQKGECFGLLGFNGAGKTTTFKMLTGEESLTSGDA
  FVGGHRISSDVGKVRQRIGYCPQFDALLDHMTGREMLVMYARLRGIPERHIGACVENTLR
  GLLLEPHANKLVRTYSGGNKRKLSTGIALIGEPAVIFLDEPSTGMDPVARRLLWDTVARA
  RESGKAIIITSHSMEECEALCTRLAIMVQGQFKCLGSPQHLKSKFGSGYSLRAKVQSEGQ
  QEALEEFKAFVDLTFPGSVLEDEHQGMVHYHLPGRDLSWAKVFGILEKAKEKYGVDDYSV
  SQISLEQVFLSFAHLQPPTAEEGR

• Sequence length: 1704