ABCA9

Summary

ABCA9 (ATP binding cassette subfamily A member 9, HGNC:39) is a protein-coding gene on chromosome 17q24.2, encoding ATP-binding cassette sub-family A member 9 (Q8IUA7). Transporter that may play a role in monocyte differentiation and lipid transport and homeostasis.

This gene is a member of the superfamily of ATP-binding cassette (ABC) transporters and the encoded protein contains two transmembrane domains and two nucleotide binding folds. 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, and White). This gene is a member of the ABC1 subfamily and is clustered with four other ABC1 family members on chromosome 17q24. Transcriptional expression of this gene is induced during monocyte differentiation into macrophages and is suppressed by cholesterol import.

Source: NCBI Gene 10350 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 243 total
• MANE Select transcript: NM_080283

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:39
Approved symbol	ABCA9
Name	ATP binding cassette subfamily A member 9
Location	17q24.2
Locus type	gene with protein product
Status	Approved
Aliases	EST640918
Ensembl gene	ENSG00000154258
Ensembl biotype	protein_coding
OMIM	612507
Entrez	10350

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000340001, ENST00000453985, ENST00000460872, ENST00000461623, ENST00000482072, ENST00000492580, ENST00000495634, ENST00000585714

RefSeq mRNA: 1 — MANE Select: NM_080283 NM_080283

CCDS: CCDS11681

Canonical transcript exons

ENST00000340001 — 39 exons

Exon	Start	End
ENSE00001014884	69020388	69020586
ENSE00001014888	68986164	68986324
ENSE00001014889	69018413	69018579
ENSE00001014892	69017656	69017789
ENSE00001014895	69011976	69012083
ENSE00001014898	69008062	69008235
ENSE00001014899	69027640	69027815
ENSE00001014901	69032108	69032276
ENSE00001014906	69033726	69033873
ENSE00001104867	68995895	68996014
ENSE00001104878	69029169	69029227
ENSE00001104907	68989027	68989118
ENSE00001104910	68993016	68993084
ENSE00001104921	69007759	69007872
ENSE00001104926	69028535	69028645
ENSE00001700840	68974488	68976013
ENSE00002443807	69026377	69026467
ENSE00002448457	69027330	69027449
ENSE00002454710	68984885	68984979
ENSE00002456941	69021742	69021861
ENSE00002486934	69024214	69024353
ENSE00002507898	68989813	68989930
ENSE00002510781	69026976	69027114
ENSE00002511572	68992175	68992266
ENSE00002533378	68985053	68985128
ENSE00002901142	69049283	69049490
ENSE00002903675	69051031	69051139
ENSE00002961687	69060866	69060927
ENSE00003462405	68990837	68990957
ENSE00003499236	69045172	69045336
ENSE00003520650	69043489	69043715
ENSE00003553476	68983709	68983849
ENSE00003589811	68984056	68984175
ENSE00003593093	69035246	69035431
ENSE00003644223	69035660	69035801
ENSE00003673237	69044497	69044600
ENSE00003683159	68976135	68976190
ENSE00003684079	69016253	69016390
ENSE00003687509	68982562	68982641

Expression profiles

Bgee: expression breadth ubiquitous, 229 present calls, max score 98.21.

FANTOM5 (CAGE): breadth broad, TPM avg 2.3254 / max 113.6806, expressed in 463 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167770	1.8953	438
167771	0.3992	174
167772	0.0243	6
167769	0.0064	4

Top tissues by expression

253 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
mucosa of stomach	UBERON:0001199	98.21	gold quality
tibial nerve	UBERON:0001323	97.50	gold quality
sural nerve	UBERON:0015488	96.41	gold quality
left ovary	UBERON:0002119	95.28	gold quality
left ventricle myocardium	UBERON:0006566	95.27	gold quality
omental fat pad	UBERON:0010414	95.20	gold quality
peritoneum	UBERON:0002358	95.14	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.46	gold quality
right ovary	UBERON:0002118	94.15	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.07	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.06	gold quality
pericardium	UBERON:0002407	93.57	gold quality
apex of heart	UBERON:0002098	92.19	gold quality
right atrium auricular region	UBERON:0006631	92.18	gold quality
cardiac atrium	UBERON:0002081	92.15	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.02	gold quality
lower esophagus	UBERON:0013473	91.94	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.91	gold quality
right lung	UBERON:0002167	91.10	gold quality
left uterine tube	UBERON:0001303	91.08	gold quality
right coronary artery	UBERON:0001625	91.08	gold quality
adipose tissue	UBERON:0001013	91.04	gold quality
ovary	UBERON:0000992	90.25	gold quality
endocervix	UBERON:0000458	89.39	gold quality
gastrocnemius	UBERON:0001388	89.35	gold quality
calcaneal tendon	UBERON:0003701	89.30	gold quality
heart	UBERON:0000948	89.11	gold quality
heart left ventricle	UBERON:0002084	88.95	gold quality
left coronary artery	UBERON:0001626	88.69	gold quality
coronary artery	UBERON:0001621	88.63	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	1652.15
E-ANND-3	yes	40.50
E-HCAD-35	yes	6.65
E-MTAB-7606	no	5.55

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• Novel key genes in triple-negative breast cancer identified by weighted gene co-expression network analysis. (PMID:31081967)
• ABCA9, an ER cholesterol transporter, inhibits breast cancer cell proliferation via SREBP-2 signaling. (PMID:36576228)

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
danio_rerio	abca5	ENSDARG00000074041
mus_musculus	Abca9	ENSMUSG00000041797
rattus_norvegicus	Abca9	ENSRNOG00000059326
drosophila_melanogaster	Eato	FBGN0028539
drosophila_melanogaster	CG1494	FBGN0031169
drosophila_melanogaster	Abca3	FBGN0031170
drosophila_melanogaster	CG1801	FBGN0031171
drosophila_melanogaster	CG8908	FBGN0034493
drosophila_melanogaster	CG6052	FBGN0036747
drosophila_melanogaster	CG31213	FBGN0051213
drosophila_melanogaster	ldd	FBGN0083956
drosophila_melanogaster	CG43672	FBGN0263747
caenorhabditis_elegans		WBGENE00000019
caenorhabditis_elegans	abt-2	WBGENE00000020
caenorhabditis_elegans		WBGENE00000022
caenorhabditis_elegans	abt-5	WBGENE00000023

Paralogs (11): ABCA7 (ENSG00000064687), ABCA2 (ENSG00000107331), ABCA8 (ENSG00000141338), ABCA12 (ENSG00000144452), ABCA6 (ENSG00000154262), ABCA10 (ENSG00000154263), ABCA5 (ENSG00000154265), ABCA1 (ENSG00000165029), ABCA3 (ENSG00000167972), ABCA13 (ENSG00000179869), ABCA4 (ENSG00000198691)

Protein

Protein identifiers

ATP-binding cassette sub-family A member 9 — Q8IUA7 (reviewed: Q8IUA7)

All UniProt accessions (3): Q8IUA7, H0Y4U7, K7EJJ0

UniProt curated annotations — full annotation on UniProt →

Function. Transporter that may play a role in monocyte differentiation and lipid transport and homeostasis.

Subcellular location. Membrane.

Tissue specificity. Widely expressed with higher expression in heart.

Induction. Up-regulated during monocyte differentiation into macrophages. Down-regulated by cholesterol loading of macrophages.

Similarity. Belongs to the ABC transporter superfamily. ABCA family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8IUA7-1	1	yes
Q8IUA7-2	2, ABCA9delta+55
Q8IUA7-3	3, ABCA9delta+73
Q8IUA7-4	4, ABCA9delta-95
Q8IUA7-5	5

RefSeq proteins (1): NP_525022* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003439	ABC_transporter-like_ATP-bd	Domain
IPR003593	AAA+_ATPase	Domain
IPR013525	ABC2_TM	Domain
IPR026082	ABCA	Family
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00005, PF12698

UniProt features (32 total): transmembrane region 14, splice variant 5, sequence variant 4, glycosylation site 3, domain 2, binding site 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IUA7-F1	77.22	0.14

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (2): 517–524; 1326–1333

Glycosylation sites (3): 120, 195, 949

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1369062	ABC transporters in lipid homeostasis
R-HSA-382551	Transport of small molecules
R-HSA-382556	ABC-family protein mediated transport

MSigDB gene sets: 91 (showing top): IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, KEGG_ABC_TRANSPORTERS, TGTGTGA_MIR377, COATES_MACROPHAGE_M1_VS_M2_UP, GOBP_LIPID_LOCALIZATION, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, CAGCCTC_MIR4855P, GOBP_TRANSMEMBRANE_TRANSPORT, GOMF_LIPID_TRANSPORTER_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES, GOMF_ACTIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_ATP_HYDROLYSIS_ACTIVITY, GOMF_ADENYL_NUCLEOTIDE_BINDING, GOMF_TRANSPORTER_ACTIVITY, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_UP

GO Biological Process (2): lipid transport (GO:0006869), transmembrane transport (GO:0055085)

GO Molecular Function (6): lipid carrier activity (GO:0005319), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), ATPase-coupled transmembrane transporter activity (GO:0042626), ABC-type transporter activity (GO:0140359), nucleotide binding (GO:0000166)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
ABC-family protein mediated transport	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
ATP-dependent activity	2
lipid localization	1
cellular process	1
molecular carrier activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
primary active transmembrane transporter activity	1
ATP hydrolysis activity	1
ATPase-coupled transmembrane transporter activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

872 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABCA9	ABCC3	O15438	459
ABCA9	ABCC9	O60706	457
ABCA9	ABCD4	O14678	443
ABCA9	ABCF3	Q9NUQ8	389
ABCA9	ABCF1	Q8NE71	362
ABCA9	OR56B4	Q8NH76	348
ABCA9	ZFAND4	Q86XD8	311
ABCA9	LYPD2	Q6UXB3	300
ABCA9	ABCA13	Q86UQ4	284
ABCA9	PCOLCE2	Q9UKZ9	282
ABCA9	ABCC8	Q09428	281
ABCA9	SLC37A3	Q8NCC5	279
ABCA9	ABCA12	Q86UK0	278
ABCA9	ABCB8	Q9NUT2	277
ABCA9	SLC16A14	Q7RTX9	274

IntAct

7 interactions, top by confidence:

A	B	Type	Score
M		psi-mi:“MI:0914”(association)	0.350
MYC		psi-mi:“MI:0914”(association)	0.350
ABCA10	POTEF	psi-mi:“MI:0914”(association)	0.350
ABCA9	SERPINB8	psi-mi:“MI:0914”(association)	0.350
ABCA9	PMM2	psi-mi:“MI:0914”(association)	0.350
ABCA9	DEDD	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): ABCA9 (Two-hybrid), ABCA9 (Affinity Capture-MS), SERPINB8 (Affinity Capture-MS), BLK (Affinity Capture-MS), GET4 (Affinity Capture-MS), PMM1 (Affinity Capture-MS), PMM2 (Affinity Capture-MS), ABCA9 (Cross-Linking-MS (XL-MS)), EEA1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A0G2K1Q8, B2RX12, E9PU17, E9PX95, F1MWM0, O00329, O15438, O35600, O75899, O88563, O88871, O94911, O95477, P41233, P55205, P58428, P78363, Q09427, Q09428, Q09429, Q2NKY8, Q5BJS0, Q5R607, Q5ZI74, Q6TL19, Q7L2E3, Q7TNJ2, Q80T41, Q84M24, Q8CF82, Q8IUA7, Q8K440, Q8K441, Q8K442, Q8K448, Q8K449, Q8LPK0, Q8N139, Q8NCL4, Q8R420

Diamond homologs: A0A059J0G5, A0A0G2K1Q8, A0A1L9WQK0, A0A1U8QKX8, A0A1U8QT10, A0A1V0QSE4, A0A1V1GB10, A0A1Y0BRF0, A0A2H1A768, A0A2U8U2K9, A0A481WQK1, A0A4P8GG95, A0A8K1AW53, A1C8C8, A1CFM0, A9YWR6, B6HV31, B6RAL1, B8NDS8, B9G5Y5, D3GE74, D4AYW0, D4GSY7, E9PU17, E9PX95, E9RBG1, F2PLH2, F2RSQ6, F2SG60, F2SHL1, G3JF11, I1RL06, J9VME1, J9VPA2, M2UCE5, O42690, O65934, O74208, O74676, P10090

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

243 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	203
Likely benign	20
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

5607 predictions. Top by Δscore:

Variant	Effect	Δscore
17:68975925:T:A	donor_gain	1.0000
17:68976011:AACC:A	acceptor_loss	1.0000
17:68976013:CCTAA:C	acceptor_loss	1.0000
17:68976014:CTAA:C	acceptor_loss	1.0000
17:68976191:C:CC	acceptor_gain	1.0000
17:68983705:CTA:C	donor_loss	1.0000
17:68983706:TACCT:T	donor_loss	1.0000
17:68983707:ACC:A	donor_loss	1.0000
17:68983708:CCT:C	donor_loss	1.0000
17:68983712:T:A	donor_gain	1.0000
17:68983845:TACAT:T	acceptor_gain	1.0000
17:68983847:CAT:C	acceptor_gain	1.0000
17:68983849:TCT:T	acceptor_loss	1.0000
17:68983850:C:CC	acceptor_gain	1.0000
17:68983850:CTGA:C	acceptor_loss	1.0000
17:68984049:CACT:C	donor_loss	1.0000
17:68984050:ACTC:A	donor_loss	1.0000
17:68984051:CTCA:C	donor_loss	1.0000
17:68984052:TCAC:T	donor_loss	1.0000
17:68984053:CACCT:C	donor_loss	1.0000
17:68984055:C:CG	donor_loss	1.0000
17:68984174:GC:G	acceptor_gain	1.0000
17:68984175:CC:C	acceptor_gain	1.0000
17:68985047:CCGTA:C	donor_loss	1.0000
17:68985048:CGTAC:C	donor_loss	1.0000
17:68985049:GTACC:G	donor_loss	1.0000
17:68985050:TA:T	donor_loss	1.0000
17:68985051:ACC:A	donor_loss	1.0000
17:68985052:C:A	donor_loss	1.0000
17:68985124:CTAAC:C	acceptor_gain	1.0000

AlphaMissense

10699 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:69016319:G:C	S991R	0.992
17:69016319:G:T	S991R	0.992
17:69016321:T:G	S991R	0.992
17:69027010:G:C	S672R	0.991
17:69027010:G:T	S672R	0.991
17:69027012:T:G	S672R	0.991
17:69035276:G:C	S366R	0.990
17:69035276:G:T	S366R	0.990
17:69035278:T:G	S366R	0.990
17:68989079:T:A	K1332I	0.988
17:69028609:G:T	A514D	0.987
17:69044511:C:G	A187P	0.987
17:69017682:C:G	A959P	0.986
17:69026410:A:G	L703P	0.986
17:69028582:T:A	K523I	0.986
17:69044536:A:C	F178L	0.985
17:69044536:A:T	F178L	0.985
17:69044538:A:G	F178L	0.985
17:69026406:C:A	K704N	0.984
17:69026406:C:G	K704N	0.984
17:69027364:A:G	L626P	0.982
17:69024243:A:G	L751S	0.981
17:69027692:A:G	L580P	0.981
17:68989075:A:C	S1333R	0.979
17:68989075:A:T	S1333R	0.979
17:68989077:T:G	S1333R	0.979
17:69016346:G:C	C982W	0.978
17:69044548:C:A	W174C	0.977
17:69044548:C:G	W174C	0.977
17:69045221:A:C	F140L	0.977

dbSNP variants (sampled 300 via entrez): RS1000031406 (17:69043311 A>G), RS1000036002 (17:69004262 G>A,T), RS1000056733 (17:69050390 A>G), RS1000121805 (17:69062869 T>C), RS1000174919 (17:69013845 T>G), RS1000220360 (17:68978781 A>G), RS1000223047 (17:68991898 A>G), RS1000240268 (17:69015649 G>C), RS1000311054 (17:69074356 C>T), RS1000321574 (17:69028880 G>A,C), RS1000344004 (17:69073969 T>A), RS1000469189 (17:68993186 C>G), RS1000485118 (17:68990478 C>G,T), RS1000527925 (17:69008648 G>C), RS1000529384 (17:69008349 C>A,T)

Disease associations

OMIM: gene MIM:612507 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST008176_4	Gestational age at birth (child effect)	5.000000e-06
GCST009533_5	Circulating leptin levels x sex interaction in high cardiovascular risk	9.000000e-06
GCST012310_10	Schizophrenia x sex interaction	3.000000e-06
GCST012311_26	Schizophrenia x sex interaction	5.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005112	gestational age
EFO:0005000	leptin measurement
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — ABCA subfamily

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
bisphenol A	increases methylation	1
lead acetate	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
manganese chloride	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
incobotulinumtoxinA	increases expression	1
Docetaxel	decreases response to substance, increases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression	1
Doxorubicin	decreases expression	1
Manganese	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.