ABCA1 (ATP binding cassette subfamily A member 1)

Gene

• Entrez ID: 19
• Gene name: ATP binding cassette subfamily A member 1
• Gene symbol: ABCA1
• Synonyms: ABC-1, ABC1, CERP, HDLCQTL13, HDLDT1, HPALP1, TGD
• Chromosome: 9
• Chromosome location: 9q31.1
• 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. With cholesterol as its substrate, this protein functions as a cholesteral efflux pump in the cellular lipid removal pathway. Mutations in both alleles of this gene cause Tangier disease and familial high-density lipoprotein (HDL) deficiency. [provided by RefSeq, Sep 2019]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs2853574	G>A	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs2853578	T>A,C	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs9282541	G>A	Conflicting-interpretations-of-pathogenicity, benign	Missense variant, non coding transcript variant, coding sequence variant
rs28933692	C>A,T	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs28937313	T>C	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs28937314	T>C,G	Likely-pathogenic, pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs35819696	T>G	Likely-benign, conflicting-interpretations-of-pathogenicity	Missense variant, non coding transcript variant, coding sequence variant
rs137854494	A>G	Pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs137854495	G>A	Pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs137854496	C>A,G	Pathogenic, uncertain-significance	Coding sequence variant, non coding transcript variant, missense variant
rs137854497	G>A	Pathogenic	Coding sequence variant, non coding transcript variant, synonymous variant, missense variant
rs137854498	G>A,T	Pathogenic	Genic downstream transcript variant, non coding transcript variant, synonymous variant, coding sequence variant, missense variant
rs137854499	A>G	Pathogenic	Coding sequence variant, non coding transcript variant, missense variant, genic downstream transcript variant
rs137854500	C>T	Pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs137854501	G>A	Pathogenic	Coding sequence variant, intron variant, missense variant, genic downstream transcript variant
rs137854502	G>T	Pathogenic	Coding sequence variant, non coding transcript variant, stop gained
rs146292819	T>G	Pathogenic	Genic downstream transcript variant, non coding transcript variant, missense variant, coding sequence variant
rs387906412	AGA>-	Pathogenic	Inframe deletion, non coding transcript variant, coding sequence variant
rs387906413	C>-	Pathogenic	Non coding transcript variant, frameshift variant, coding sequence variant
rs387906414	AG>-	Pathogenic	Non coding transcript variant, frameshift variant, coding sequence variant
rs387906415	GGCG>-	Pathogenic	Non coding transcript variant, frameshift variant, coding sequence variant
rs760507032	G>C	Pathogenic	Coding sequence variant, non coding transcript variant, missense variant, genic downstream transcript variant
rs762770081	C>T	Likely-pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs796051872	C>G	Pathogenic	Splice donor variant
rs796051873	AGAACTTCCTCTCA>GTACAGTGGCGTGACCTCAGCTCACTGCAACCTCTGCCTCCTGAGTTCAAGTGATTCTCGTGCCTCAGCCTCCCAAGTAGCTGGGATT,GTACAGTGGCGTGACCTCAGCTCACTGCAACCTCTGCCTCCTGAGTTCAAGTGATTCTCGTGCCTCAGCCTCCCAAGTAGCTGGGATTACAGCTCCTGCCACCACGCCCG	Pathogenic	Inframe indel, coding sequence variant, non coding transcript variant, stop gained
rs1554696687	C>A	Pathogenic	Genic downstream transcript variant, splice acceptor variant
rs1554714092	G>-	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT003670	hsa-miR-33b-5p	Luciferase reporter assay	20466882
MIRT003672	hsa-miR-33a-5p	Luciferase reporter assay	20466885
MIRT003672	hsa-miR-33a-5p	Luciferase reporter assay	20466882
MIRT003672	hsa-miR-33a-5p	Luciferase reporter assay	20566875
MIRT006711	hsa-miR-26a-5p	Immunoblot, Luciferase reporter assay, qRT-PCR	22673513
MIRT006713	hsa-miR-26b-5p	Immunoblot, Luciferase reporter assay, qRT-PCR	22673513
MIRT006713	hsa-miR-26b-5p	Microarray	19088304
MIRT007121	hsa-miR-19a-3p	Luciferase reporter assay	23451058
MIRT007123	hsa-miR-27a-3p	Luciferase reporter assay	23451058
MIRT007123	hsa-miR-27a-3p	Luciferase reporter assay, qRT-PCR, Western blot	24608080
MIRT054227	hsa-miR-128-3p	Luciferase reporter assay, Microarray, qRT-PCR, Western blot	23990020
MIRT054624	hsa-miR-27b-3p	Luciferase reporter assay, qRT-PCR, Western blot	24608080
MIRT054624	hsa-miR-27b-3p	Luciferase reporter assay, qRT-PCR, Western blot	26520906
MIRT437926	hsa-miR-613	qRT-PCR, Luciferase reporter assay, Western blot	24751522
MIRT441312	hsa-miR-20a-5p	HITS-CLIP	22473208
MIRT441313	hsa-miR-106b-5p	HITS-CLIP	22473208
MIRT728414	hsa-miR-519d-3p	HITS-CLIP	22473208
MIRT728415	hsa-miR-93-5p	HITS-CLIP	22473208
MIRT728415	hsa-miR-93-5p	ELISA, Luciferase reporter assay, qRT-PCR, Western blot	25785043
MIRT728416	hsa-miR-17-5p	HITS-CLIP	22473208
MIRT728416	hsa-miR-17-5p	ELISA, Luciferase reporter assay, qRT-PCR, Western blot	25785043
MIRT728417	hsa-miR-20b-5p	HITS-CLIP	22473208
MIRT733405	hsa-miR-33a-3p	qRT-PCR, Western blot	26945479
MIRT733405	hsa-miR-33a-3p	ELISA, qRT-PCR	27664032
MIRT733858	hsa-miR-33b-3p	qRT-PCR	27301461
MIRT734877	hsa-miR-148a-5p	Luciferase reporter assay, Northern blot, qRT-PCR, Western blot	26437365
MIRT735363	hsa-miR-302a-3p	Luciferase reporter assay, qRT-PCR, Western blot	25524771

Transcription factors

Transcription factor	Regulation	Reference
FOXA1	Repression	24807696
FOXA2	Repression	24807696
NFKB1	Repression	17135302
NR1H2	Activation	16141411
NR1H3	Activation	11264984;16141411;18580406;19201410
NR1H3	Unknown	15171719
RELA	Repression	17135302
RXRA	Activation	14764426
SP1	Activation	11264984;17887732
SP1	Unknown	10884428
SP3	Repression	15922656
SP3	Unknown	10884428
SREBF2	Repression	15922656;16901265
STAT3	Unknown	19783654
USF1	Activation	11861672
USF2	Activation	11861672
ZNF202	Repression	15922656

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005102	Function	Signaling receptor binding	IPI	23931754
GO:0005319	Function	Lipid transporter activity	IBA	21873635
GO:0005515	Function	Protein binding	IPI	12084722, 14754908, 15469992, 16192269, 16443932, 23931754, 25170080, 30458687
GO:0005524	Function	ATP binding	IDA	11700048
GO:0005548	Function	Phospholipid transporter activity	IGI	28373057
GO:0005768	Component	Endosome	IDA	24097981
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0005886	Component	Plasma membrane	IDA	19556522, 23931754, 24097981, 28373057
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	IDA	10525055
GO:0006869	Process	Lipid transport	IBA	21873635
GO:0007040	Process	Lysosome organization	IDA	15163665
GO:0007186	Process	G protein-coupled receptor signaling pathway	IMP	16443932
GO:0007189	Process	Adenylate cyclase-activating G protein-coupled receptor signaling pathway	IMP	14701824
GO:0008203	Process	Cholesterol metabolic process	IDA	14747463
GO:0008320	Function	Protein transmembrane transporter activity	ISS	29937375
GO:0009306	Process	Protein secretion	IMP	11855831
GO:0009306	Process	Protein secretion	ISS	29937375
GO:0010745	Process	Negative regulation of macrophage derived foam cell differentiation	TAS	18490524
GO:0010875	Process	Positive regulation of cholesterol efflux	IMP	25084135
GO:0010887	Process	Negative regulation of cholesterol storage	TAS	18490524
GO:0015485	Function	Cholesterol binding	IC	12084722
GO:0016197	Process	Endosomal transport	IDA	14747463
GO:0016887	Function	ATPase activity	IEA
GO:0019216	Process	Regulation of lipid metabolic process	TAS
GO:0019905	Function	Syntaxin binding	IPI	15469992
GO:0023061	Process	Signal release	IMP	11855831
GO:0023061	Process	Signal release	ISS	29937375
GO:0030139	Component	Endocytic vesicle	IDA	14747463
GO:0031210	Function	Phosphatidylcholine binding	IDA	24097981
GO:0031267	Function	Small GTPase binding	IPI	16443932
GO:0032367	Process	Intracellular cholesterol transport	IMP	10431236
GO:0032489	Process	Regulation of Cdc42 protein signal transduction	IMP	16443932
GO:0033344	Process	Cholesterol efflux	IDA	10431236, 11162594, 16702602, 23931754
GO:0033344	Process	Cholesterol efflux	IGI	28373057
GO:0033344	Process	Cholesterol efflux	IMP	16443932, 19556522
GO:0033700	Process	Phospholipid efflux	IBA	21873635
GO:0033700	Process	Phospholipid efflux	IDA	10431236, 11162594
GO:0033700	Process	Phospholipid efflux	IGI	28373057
GO:0033700	Process	Phospholipid efflux	IMP	16702602, 19556522
GO:0034185	Function	Apolipoprotein binding	IPI	11162594
GO:0034186	Function	Apolipoprotein A-I binding	IPI	11162594, 16443932
GO:0034188	Function	Apolipoprotein A-I receptor activity	IDA	16443932
GO:0034380	Process	High-density lipoprotein particle assembly	IMP	10431236, 14754908, 17305370
GO:0034380	Process	High-density lipoprotein particle assembly	TAS
GO:0034616	Process	Response to laminar fluid shear stress	IDA	15358760
GO:0038027	Process	Apolipoprotein A-I-mediated signaling pathway	IEA
GO:0042626	Function	ATPase-coupled transmembrane transporter activity	IBA	21873635
GO:0042632	Process	Cholesterol homeostasis	IDA	10431236
GO:0042632	Process	Cholesterol homeostasis	TAS	24097981
GO:0043231	Component	Intracellular membrane-bounded organelle	IBA	21873635
GO:0043691	Process	Reverse cholesterol transport	IMP	10431236
GO:0045121	Component	Membrane raft	IDA	15469992
GO:0045332	Process	Phospholipid translocation	IDA	24097981
GO:0045335	Component	Phagocytic vesicle	IDA	15469992
GO:0046623	Function	Sphingolipid floppase activity	IDA	24097981
GO:0048471	Component	Perinuclear region of cytoplasm	IDA	23931754
GO:0051117	Function	ATPase binding	IPI	23931754
GO:0055091	Process	Phospholipid homeostasis	IMP	16702602
GO:0060155	Process	Platelet dense granule organization	IMP	15163665
GO:0071404	Process	Cellular response to low-density lipoprotein particle stimulus	NAS	15358760
GO:0071806	Process	Protein transmembrane transport	ISS	29937375
GO:0090107	Process	Regulation of high-density lipoprotein particle assembly	TAS	24097981
GO:0090108	Process	Positive regulation of high-density lipoprotein particle assembly	ISS
GO:0090554	Function	Phosphatidylcholine floppase activity	IBA	21873635
GO:0090554	Function	Phosphatidylcholine floppase activity	IDA	16702602, 24097981
GO:0090556	Function	Phosphatidylserine floppase activity	IBA	21873635
GO:0090556	Function	Phosphatidylserine floppase activity	IDA	24097981
GO:0097708	Component	Intracellular vesicle	IDA	28373057
GO:0099039	Process	Sphingolipid translocation	IEA
GO:0120009	Process	Intermembrane lipid transfer	IEA
GO:0120020	Function	Cholesterol transfer activity	IDA	12084722
GO:0140115	Process	Export across plasma membrane	ISS	29937375
GO:0140328	Function	Floppase activity	IDA	16702602, 24097981

Other IDs

• MIM: 600046
• HGNC: 29
• e!Ensembl: ENSG00000165029

Protein

• UniProt ID: O95477
• Protein name: Phospholipid-transporting ATPase ABCA1 (EC 7.6.2.1) (ATP-binding cassette sub-family A member 1) (ATP-binding cassette transporter 1) (ABC-1) (ATP-binding cassette 1) (Cholesterol efflux regulatory protein)
• Protein function: Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981). Thereby, participates in phospholipid transfer to apoliproteins to form nascent high density lipoproteins/HDLs (PubMed:14754908). Transports preferentially phosphatidylcholine over phosphatidylserine (PubMed:24097981). May play a similar role in the efflux of intracellular cholesterol to apoliproteins and the formation of nascent high density lipoproteins/HDLs (PubMed:10533863, PubMed:14754908, PubMed:24097981).
• PDB: 5XJY
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF12698	ABC2_membrane_3	594 → 841		Family
  PF00005	ABC_tran	916 → 1061	ABC transporter	Domain
  PF12698	ABC2_membrane_3	1344 → 1869		Family
  PF00005	ABC_tran	1929 → 2073	ABC transporter	Domain

• Sequence:

  MACWPQLRLLLWKNLTFRRRQTCQLLLEVAWPLFIFLILISVRLSYPPYEQHECHFPNKA
  MPSAGTLPWVQGIICNANNPCFRYPTPGEAPGVVGNFNKSIVARLFSDARRLLLYSQKDT
  SMKDMRKVLRTLQQIKKSSSNLKLQDFLVDNETFSGFLYHNLSLPKSTVDKMLRADVILH
  KVFLQGYQLHLTSLCNGSKSEEMIQLGDQEVSELCGLPREKLAAAERVLRSNMDILKPIL
  RTLNSTSPFPSKELAEATKTLLHSLGTLAQELFSMRSWSDMRQEVMFLTNVNSSSSSTQI
  YQAVSRIVCGHPEGGGLKIKSLNWYEDNNYKALFGGNGTEEDAETFYDNSTTPYCNDLMK
  NLESSPLSRIIWKALKPLLVGKILYTPDTPATRQVMAEVNKTFQELAVFHDLEGMWEELS
  PKIWTFMENSQEMDLVRMLLDSRDNDHFWEQQLDGLDWTAQDIVAFLAKHPEDVQSSNGS
  VYTWREAFNETNQAIRTISRFMECVNLNKLEPIATEVWLINKSMELLDERKFWAGIVFTG
  ITPGSIELPHHVKYKIRMDIDNVERTNKIKDGYWDPGPRADPFEDMRYVWGGFAYLQDVV
  EQAIIRVLTGTEKKTGVYMQQMPYPCYVDDIFLRVMSRSMPLFMTLAWIYSVAVIIKGIV
  YEKEARLKETMRIMGLDNSILWFSWFISSLIPLLVSAGLLVVILKLGNLLPYSDPSVVFV
  FLSVFAVVTILQCFLISTLFSRANLAAACGGIIYFTLYLPYVLCVAWQDYVGFTLKIFAS
  LLSPVAFGFGCEYFALFEEQGIGVQWDNLFESPVEEDGFNLTTSVSMMLFDTFLYGVMTW
  YIEAVFPGQYGIPRPWYFPCTKSYWFGEESDEKSHPGSNQKRISEICMEEEPTHLKLGVS
  IQNLVKVYRDGMKVAVDGLALNFYEGQITSFLGHNGAGKTTTMSILTGLFPPTSGTAYIL
  GKDIRSEMSTIRQNLGVCPQHNVLFDMLTVEEHIWFYARLKGLSEKHVKAEMEQMALDVG
  LPSSKLKSKTSQLSGGMQRKLSVALAFVGGSKVVILDEPTAGVDPYSRRGIWELLLKYRQ
  GRTIILSTHHMDEADVLGDRIAIISHGKLCCVGSSLFLKNQLGTGYYLTLVKKDVESSLS
  SCRNSSSTVSYLKKEDSVSQSSSDAGLGSDHESDTLTIDVSAISNLIRKHVSEARLVEDI
  GHELTYVLPYEAAKEGAFVELFHEIDDRLSDLGISSYGISETTLEEIFLKVAEESGVDAE
  TSDGTLPARRNRRAFGDKQSCLRPFTEDDAADPNDSDIDPESRETDLLSGMDGKGSYQVK
  GWKLTQQQFVALLWKRLLIARRSRKGFFAQIVLPAVFVCIALVFSLIVPPFGKYPSLELQ
  PWMYNEQYTFVSNDAPEDTGTLELLNALTKDPGFGTRCMEGNPIPDTPCQAGEEEWTTAP
  VPQTIMDLFQNGNWTMQNPSPACQCSSDKIKKMLPVCPPGAGGLPPPQRKQNTADILQDL
  TGRNISDYLVKTYVQIIAKSLKNKIWVNEFRYGGFSLGVSNTQALPPSQEVNDAIKQMKK
  HLKLAKDSSADRFLNSLGRFMTGLDTKNNVKVWFNNKGWHAISSFLNVINNAILRANLQK
  GENPSHYGITAFNHPLNLTKQQLSEVALMTTSVDVLVSICVIFAMSFVPASFVVFLIQER
  VSKAKHLQFISGVKPVIYWLSNFVWDMCNYVVPATLVIIIFICFQQKSYVSSTNLPVLAL
  LLLLYGWSITPLMYPASFVFKIPSTAYVVLTSVNLFIGINGSVATFVLELFTDNKLNNIN
  DILKSVFLIFPHFCLGRGLIDMVKNQAMADALERFGENRFVSPLSWDLVGRNLFAMAVEG
  VVFFLITVLIQYRFFIRPRPVNAKLSPLNDEDEDVRRERQRILDGGGQNDILEIKELTKI
  YRRKRKPAVDRICVGIPPGECFGLLGVNGAGKSSTFKMLTGDTTVTRGDAFLNKNSILSN
  IHEVHQNMGYCPQFDAITELLTGREHVEFFALLRGVPEKEVGKVGEWAIRKLGLVKYGEK
  YAGNYSGGNKRKLSTAMALIGGPPVVFLDEPTTGMDPKARRFLWNCALSVVKEGRSVVLT
  SHSMEECEALCTRMAIMVNGRFRCLGSVQHLKNRFGDGYTIVVRIAGSNPDLKPVQDFFG
  LAFPGSVLKEKHRNMLQYQLPSSLSSLARIFSILSQSKKRLHIEDYSVSQTTLDQVFVNF
  AKDQSDDDHLKDLSLHKNQTVVDVAVLTSFLQDEKVKESYV

• Sequence length: 2261