ABCA2

Summary

ABCA2 (ATP binding cassette subfamily A member 2, HGNC:32) is a protein-coding gene on chromosome 9q34.3, encoding ATP-binding cassette sub-family A member 2 (Q9BZC7). Probable lipid transporter that modulates cholesterol sequestration in the late endosome/lysosome by regulating the intracellular sphingolipid metabolism, in turn participates in cholesterol homeostasis.

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. This protein is highly expressed in brain tissue and may play a role in macrophage lipid metabolism and neural development. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 20 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual developmental disorder with poor growth and with or without seizures or ataxia (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 7
• Clinical variants (ClinVar): 712 total — 37 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 15
• MANE Select transcript: NM_001606

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32
Approved symbol	ABCA2
Name	ATP binding cassette subfamily A member 2
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000107331
Ensembl biotype	protein_coding
OMIM	600047
Entrez	20

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 12 retained_intron, 6 protein_coding, 4 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000341511, ENST00000371605, ENST00000398207, ENST00000425423, ENST00000431584, ENST00000437791, ENST00000459850, ENST00000463603, ENST00000464157, ENST00000464520, ENST00000464876, ENST00000466707, ENST00000467624, ENST00000470535, ENST00000476211, ENST00000479446, ENST00000487109, ENST00000488535, ENST00000490486, ENST00000492260, ENST00000494046, ENST00000614293, ENST00000970112, ENST00000970113

RefSeq mRNA: 3 — MANE Select: NM_001606 NM_001411042, NM_001606, NM_212533

CCDS: CCDS43909, CCDS94538, CCDS94539

Canonical transcript exons

ENST00000341511 — 49 exons

Exon	Start	End
ENSE00001896071	137028075	137028237
ENSE00002388811	137007234	137007964
ENSE00003467947	137009769	137009903
ENSE00003468343	137009370	137009462
ENSE00003469067	137008951	137009053
ENSE00003477159	137020336	137020495
ENSE00003483574	137022351	137022478
ENSE00003488667	137018719	137018815
ENSE00003495699	137011634	137011749
ENSE00003496502	137015675	137015871
ENSE00003500386	137010193	137010371
ENSE00003501850	137011844	137012018
ENSE00003509459	137023838	137023840
ENSE00003534314	137015414	137015596
ENSE00003552989	137011186	137011309
ENSE00003565680	137020694	137021061
ENSE00003570673	137010973	137011105
ENSE00003570708	137009983	137010124
ENSE00003585753	137012712	137012925
ENSE00003592816	137012265	137012376
ENSE00003593685	137014913	137015097
ENSE00003593971	137008731	137008868
ENSE00003593988	137019178	137019306
ENSE00003596227	137012102	137012162
ENSE00003606038	137018903	137019070
ENSE00003620979	137010620	137010737
ENSE00003622925	137008416	137008622
ENSE00003631260	137021392	137021610
ENSE00003632119	137015962	137016174
ENSE00003638712	137014168	137014404
ENSE00003639854	137024143	137024236
ENSE00003651508	137013002	137013318
ENSE00003664937	137009541	137009644
ENSE00003676339	137013832	137014038
ENSE00003680661	137013461	137013563
ENSE00003687525	137012485	137012590
ENSE00003689149	137014690	137014810
ENSE00003689875	137022702	137022865
ENSE00003690904	137021891	137022001
ENSE00003755406	137011407	137011554
ENSE00003756831	137017973	137018075
ENSE00003757303	137017787	137017901
ENSE00003757434	137017502	137017692
ENSE00003758458	137016291	137016471
ENSE00003759083	137018178	137018351
ENSE00003759124	137016574	137016738
ENSE00003759532	137017196	137017346
ENSE00003760265	137016920	137017124
ENSE00003786755	137022941	137023052

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 99.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.4319 / max 1132.5932, expressed in 1656 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103279	10.6447	1529
103278	3.3318	464
103280	1.0946	615
103282	1.0360	260
103281	0.7211	363
103284	0.2637	151
103272	0.2384	94
103264	0.1686	37
103270	0.1674	68
103263	0.1560	45

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	99.68	gold quality
spinal cord	UBERON:0002240	99.23	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.21	gold quality
right frontal lobe	UBERON:0002810	99.09	gold quality
peripheral nervous system	UBERON:0000010	98.99	gold quality
nerve	UBERON:0001021	98.99	gold quality
tibial nerve	UBERON:0001323	98.99	gold quality
cerebellar hemisphere	UBERON:0002245	98.95	gold quality
cerebellar cortex	UBERON:0002129	98.86	gold quality
middle frontal gyrus	UBERON:0002702	98.83	gold quality
amygdala	UBERON:0001876	98.24	gold quality
inferior vagus X ganglion	UBERON:0005363	98.14	gold quality
prefrontal cortex	UBERON:0000451	97.89	gold quality
hypothalamus	UBERON:0001898	97.85	gold quality
sural nerve	UBERON:0015488	97.85	gold quality
corpus callosum	UBERON:0002336	97.82	gold quality
cingulate cortex	UBERON:0003027	97.76	gold quality
anterior cingulate cortex	UBERON:0009835	97.75	gold quality
nucleus accumbens	UBERON:0001882	97.71	gold quality
adenohypophysis	UBERON:0002196	97.58	gold quality
granulocyte	CL:0000094	97.43	gold quality
caudate nucleus	UBERON:0001873	97.39	gold quality
cerebellum	UBERON:0002037	97.32	gold quality
putamen	UBERON:0001874	96.86	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.38	gold quality
Ammon’s horn	UBERON:0001954	96.24	gold quality
pituitary gland	UBERON:0000007	96.23	gold quality
frontal cortex	UBERON:0001870	95.97	gold quality
inferior olivary complex	UBERON:0002127	95.92	gold quality
medulla oblongata	UBERON:0001896	95.87	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	1121.78
E-HCAD-25	yes	56.03
E-GEOD-84465	yes	11.16
E-ANND-3	yes	3.77
E-MTAB-6386	no	87.02

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF, EGR1, SP1, SP3, SP4

miRNA regulators (miRDB)

44 targeting ABCA2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-7112-5P	99.59	65.76	104
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-4722-3P	99.35	65.22	1099
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-4763-3P	99.10	67.83	2649

Literature-anchored findings (GeneRIF, showing 20)

• The Stoned proteins may regulate sustainable neurotransmission in vivo by binding to Ca(2+)-bound Synaptotagmin-1 associated synaptic vesicles. (PMID:22701718)
• roles for this largest known ABC protein in neural transmembrane lipid export (PMID:12363033)
• Reciprocal regulation of expression of the ABCA2 promoter by the early growth response-1 and Sp-family transcription factors. (PMID:12560508)
• It is likely that expression of ABCA2 by two independent promoters constitutes locus of regulation controlling expression of the protein to meet requirements in different tissues. (PMID:15093135)
• Increased expression of ABCA2 may be causally linked with altered expression of genes associated with the pathogenesis of Alzheimer disease. (PMID:15155565)
• Among the 45 ABCA2 single nucleotide polymorphisms(SNPs) we tested, one synonymous SNP (rs908832) was found significantly associated with AD in both samples. (PMID:15649702)
• the expression patterns of ABCA2 in combination with other markers showed phenotypic heterogeneity in schwannomas (PMID:15850583)
• Data suggest that ABCA2 may exert population-dependent effects on the genetic risk for sporadic Alzheimer’s disease and support a role of ABC lipid transporters in the pathogenesis of this disease. (PMID:16752360)
• No association of ABCA2 Single Nucleotide Polymorphism on chromosome 9 with Alzheimer’s disease. (PMID:18336955)
• A possible biochemical mechanism links ABCA2 expression, amyloid precursor protein processing, and Alzheimer’s disease. (PMID:20704561)
• we demonstrate that ABCA2-deficiency inhibits prostate tumor metastasis in vivo and decreases chemotactic potential of cells (PMID:21041019)
• SLC2A1/GLUT1, SLC1A3/EAAT1, and SLC1A2/EAAT2 were the main SLC proteins whereas ABCG2/BCRP, ABCB1/MDR1, ABCA2 and ABCA8 were the main ABC quantified in isolated brain microvessels (PMID:21707071)
• Down-regulation of the ATP-binding cassette transporter 2 (Abca2) reduces amyloid-beta production by altering Nicastrin maturation and intracellular localization. (PMID:22086926)
• Our findings indicate a considerable and direct relationship between mRNA expression levels of ABCA2, ABCA3, MDR1, and MRP1 genes and positive minimal residual disease (MRD) measured after one year of treatment. (PMID:24145140)
• The analyses results suggested ABCA2 mRNA expression was upregulated significantly in AD compared with controls in all datasets. (PMID:29224028)
• High expression of ABCA2 is associated with drug resistance in pediatric acute lymphoblastic leukemia. (PMID:29630744)
• Results from a Genome-Wide Association Study (GWAS) in Mastocytosis Reveal New Gene Polymorphisms Associated with WHO Subgroups. (PMID:32752121)
• Role of ABCA2 and its single nucleotide polymorphisms (4873T>A and 4879G>C) in the regulation of multi-drug resistance in oral squamous carcinoma cells. (PMID:37167718)
• A polymorphism in ABCA2 is associated with neutropenia induced by capecitabine in Japanese patients with colorectal cancer. (PMID:37653272)
• Novel compound heterozygous ABCA2 variants cause IDPOGSA, a variable phenotypic syndrome with intellectual disability. (PMID:38228874)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	abca2	ENSDARG00000013500
mus_musculus	Abca2	ENSMUSG00000026944
rattus_norvegicus	Abca2	ENSRNOG00000014268
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
caenorhabditis_elegans		WBGENE00000019
caenorhabditis_elegans	abt-2	WBGENE00000020
caenorhabditis_elegans		WBGENE00000022
caenorhabditis_elegans	abt-5	WBGENE00000023

Paralogs (11): ABCA7 (ENSG00000064687), ABCA8 (ENSG00000141338), ABCA12 (ENSG00000144452), ABCA9 (ENSG00000154258), ABCA6 (ENSG00000154262), ABCA10 (ENSG00000154263), ABCA5 (ENSG00000154265), ABCA1 (ENSG00000165029), ABCA3 (ENSG00000167972), ABCA13 (ENSG00000179869), ABCA4 (ENSG00000198691)

Protein

Protein identifiers

ATP-binding cassette sub-family A member 2 — Q9BZC7 (reviewed: Q9BZC7)

Alternative names: ATP-binding cassette transporter 2

All UniProt accessions (7): Q9BZC7, A0A087WXK5, E9PGB2, H0Y8C9, H0Y8D6, H0Y8E3, H7C5M6

UniProt curated annotations — full annotation on UniProt →

Function. Probable lipid transporter that modulates cholesterol sequestration in the late endosome/lysosome by regulating the intracellular sphingolipid metabolism, in turn participates in cholesterol homeostasis. May alter the transbilayer distribution of ceramide in the intraluminal membrane lipid bilayer, favoring its retention in the outer leaflet that results in increased acid ceramidase activity in the late endosome/lysosome, facilitating ceramide deacylation to sphingosine leading to the sequestration of free cholesterol in lysosomes. In addition regulates amyloid-beta production either by activating a signaling pathway that regulates amyloid precursor protein transcription through the modulation of sphingolipid metabolism or through its role in gamma-secretase processing of APP. May play a role in myelin formation.

Subcellular location. Endosome membrane. Lysosome membrane.

Tissue specificity. Highly expressed in the brain,peripheral blood leukocytes and ovary, whereas lower levels of expression is observed in kidney and liver. Weakly expressed in brain and highly in peripheral blood leukocytes.

Post-translational modifications. Methylated at Gln-271 by N6AMT1.

Disease relevance. Intellectual developmental disorder with poor growth and with or without seizures or ataxia (IDPOGSA) [MIM:618808] An autosomal recessive disorder characterized by global developmental delay apparent from infancy, impaired intellectual development, hypotonia, and poor overall growth with microcephaly. Additional variable features include dysmorphic features, cataracts, ataxia and seizures. The disease is caused by variants affecting the gene represented in this entry.

Induction. Increased under sterol-deprived conditions and decreased by the addition of exogenous sterols.

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q9BZC7-1	1	yes
Q9BZC7-2	2
Q9BZC7-3	3, 1A form
Q9BZC7-4	4, 1B form

RefSeq proteins (3): NP_001397971, NP_001597, NP_997698 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003439	ABC_transporter-like_ATP-bd	Domain
IPR003593	AAA+_ATPase	Domain
IPR013525	ABC2_TM	Domain
IPR017871	ABC_transporter-like_CS	Conserved_site
IPR026082	ABCA	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR056264	R2_ABCA1-4-like	Domain

Pfam: PF00005, PF12698, PF23321

UniProt features (64 total): glycosylation site 25, transmembrane region 14, modified residue 5, splice variant 4, region of interest 3, sequence variant 3, domain 2, compositionally biased region 2, binding site 2, sequence conflict 2, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BZC7-F1	71.46	0.10

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): 1024–1031; 2087–2094

Post-translational modifications (5): 271, 1238, 1327, 1331, 2412

Glycosylation sites (25): 14, 89, 168, 173, 305, 368, 379, 420, 432, 476, 484, 494, 530, 544, 590, 600, 628, 1408, 1496, 1549 …

Mutagenesis-validated functional residues (1):

Position	Phenotype
271	abolishes methylation by n6amt1.

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: 366 (showing top): AP1_01, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_BEHAVIOR, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_STEROL_HOMEOSTASIS, GOCC_VACUOLAR_MEMBRANE, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_AMIDE_METABOLIC_PROCESS, GOBP_SPHINGOMYELIN_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GOBP_POLYOL_METABOLIC_PROCESS, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_NEGATIVE_REGULATION_OF_STEROID_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS

GO Biological Process (36): ganglioside metabolic process (GO:0001573), lipid metabolic process (GO:0006629), sphingomyelin metabolic process (GO:0006684), glycosphingolipid metabolic process (GO:0006687), lipid transport (GO:0006869), locomotory behavior (GO:0007626), response to xenobiotic stimulus (GO:0009410), regulation of steroid metabolic process (GO:0019218), central nervous system myelin formation (GO:0032289), regulation of intracellular cholesterol transport (GO:0032383), negative regulation of intracellular cholesterol transport (GO:0032384), positive regulation of low-density lipoprotein particle receptor catabolic process (GO:0032805), cholesterol homeostasis (GO:0042632), positive regulation of amyloid precursor protein biosynthetic process (GO:0042986), negative regulation of steroid metabolic process (GO:0045939), sphingosine biosynthetic process (GO:0046512), response to steroid hormone (GO:0048545), transmembrane transport (GO:0055085), response to cholesterol (GO:0070723), negative regulation of phospholipid biosynthetic process (GO:0071072), negative regulation of sphingolipid biosynthetic process (GO:0090155), intracellular sphingolipid homeostasis (GO:0090156), negative regulation of cholesterol efflux (GO:0090370), ceramide translocation (GO:0099040), transport across blood-brain barrier (GO:0150104), regulation of post-translational protein modification (GO:1901873), positive regulation of amyloid-beta formation (GO:1902004), positive regulation of amyloid precursor protein catabolic process (GO:1902993), regulation of protein localization to cell periphery (GO:1904375), negative regulation of receptor-mediated endocytosis involved in cholesterol transport (GO:1905601), regulation of protein localization to cell surface (GO:2000008), regulation of macromolecule biosynthetic process (GO:0010556), lipid translocation (GO:0034204), regulation of protein metabolic process (GO:0051246), positive regulation of protein metabolic process (GO:0051247), obsolete regulation of protein glycosylation (GO:0060049)

GO Molecular Function (9): nucleotide binding (GO:0000166), lipid carrier activity (GO:0005319), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), ATPase-coupled transmembrane transporter activity (GO:0042626), endopeptidase regulator activity (GO:0061135), ceramide floppase activity (GO:0099038), ABC-type transporter activity (GO:0140359), floppase activity (GO:0140328)

GO Cellular Component (10): lysosome (GO:0005764), lysosomal membrane (GO:0005765), endosome (GO:0005768), microtubule organizing center (GO:0005815), plasma membrane (GO:0005886), endosome membrane (GO:0010008), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), ATP-binding cassette (ABC) transporter complex (GO:0043190), cytoplasm (GO:0005737)

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
cellular anatomical structure	3
sphingolipid metabolic process	2
transport	2
steroid metabolic process	2
intracellular cholesterol transport	2
ATP-dependent activity	2
ceramide metabolic process	1
glycosphingolipid metabolic process	1
primary metabolic process	1
phospholipid metabolic process	1
glycolipid metabolic process	1
lipid localization	1
behavior	1
response to chemical	1
regulation of lipid metabolic process	1
central nervous system myelination	1
myelin assembly	1
regulation of cholesterol transport	1
regulation of intracellular sterol transport	1
negative regulation of cholesterol transport	1
negative regulation of intracellular sterol transport	1
regulation of intracellular cholesterol transport	1
low-density lipoprotein particle receptor catabolic process	1
regulation of low-density lipoprotein particle receptor catabolic process	1
positive regulation of protein catabolic process	1
positive regulation of receptor catabolic process	1
sterol homeostasis	1
positive regulation of glycoprotein biosynthetic process	1
amyloid precursor protein biosynthetic process	1
regulation of amyloid precursor protein biosynthetic process	1
regulation of steroid metabolic process	1
negative regulation of lipid metabolic process	1
sphingosine metabolic process	1
diol biosynthetic process	1
sphingoid biosynthetic process	1
response to hormone	1
response to lipid	1
cellular process	1
response to sterol	1
response to alcohol	1

Protein interactions and networks

STRING

1352 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABCA2	ELP6	Q0PNE2	738
ABCA2	CYP46A1	Q9Y6A2	622
ABCA2	ABCC3	O15438	598
ABCA2	HMGCS1	Q01581	591
ABCA2	BLMH	Q13867	515
ABCA2	ABCB1	P08183	508
ABCA2	ABCF1	Q8NE71	490
ABCA2	ABCD4	O14678	490
ABCA2	APP	P05067	483
ABCA2	APOA1	P02647	475
ABCA2	CCDC183	Q5T5S1	469
ABCA2	GSTO1	P78417	455
ABCA2	APBB2	Q92870	455
ABCA2	HSD11B1	P28845	448
ABCA2	MAMDC4	Q6UXC1	443

IntAct

202 interactions, top by confidence:

A	B	Type	Score
YWHAH	FAM83G	psi-mi:“MI:0914”(association)	0.710
FBXO6	MAN2B1	psi-mi:“MI:0914”(association)	0.640
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
BTNL3	FAM171A2	psi-mi:“MI:0914”(association)	0.530
ZNRF4	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
CLGN	NPC1	psi-mi:“MI:0914”(association)	0.530
VAMP5	NBAS	psi-mi:“MI:0914”(association)	0.530
MRAP2	PODXL	psi-mi:“MI:0914”(association)	0.530
PON2	NPC1	psi-mi:“MI:0914”(association)	0.530
LGALS1	LAMA5	psi-mi:“MI:0914”(association)	0.530
C1orf54	EXTL3	psi-mi:“MI:0914”(association)	0.530
ABCA2	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
HTRA3	ABCA2	psi-mi:“MI:0407”(direct interaction)	0.440
ABCA2	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
ABCA2	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
ABCA2	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
ABCA2	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
ABCA2	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
ABCA2	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
ABCA2	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
ABCA2	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
ABCA2	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
ABCA2	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.440
ABCA2	FRMPD4	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	ABCA2	psi-mi:“MI:0407”(direct interaction)	0.440
ABCA2	LIN7C	psi-mi:“MI:0407”(direct interaction)	0.440
MAGI3	ABCA2	psi-mi:“MI:0407”(direct interaction)	0.440
ABCA2	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (124): ABCA2 (Affinity Capture-RNA), ABCA2 (Affinity Capture-MS), ABCA2 (Affinity Capture-MS), ABCA2 (Affinity Capture-MS), ABCA2 (Affinity Capture-MS), ABCA2 (Affinity Capture-MS), ABCA2 (Affinity Capture-MS), ABCA2 (Affinity Capture-MS), ABCA2 (Affinity Capture-MS), ABCA2 (Affinity Capture-MS), ABCA2 (Affinity Capture-MS), ABCA2 (Affinity Capture-MS), ABCA2 (Affinity Capture-MS), ABCA2 (Affinity Capture-MS), ABCA2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2K1Q8, A0A1D5PXA5, B5DFM7, E1B9E5, E9PU17, E9PX95, E9Q9F6, F1MWM0, F1QYC4, H2L0G5, O35600, O95477, P0DP43, P41233, P41234, P78363, Q09614, Q11204, Q1PEH6, Q3TT99, Q3V5L5, Q64663, Q6W3E5, Q765H6, Q84M24, Q86XM0, Q8IMZ9, Q8K440, Q8K442, Q8K449, Q8LPK0, Q8R420, Q91WD2, Q95JI2, Q95JR7, Q99572, Q99758, Q9BZC7, Q9EPK8, Q9ERZ8

Diamond homologs: A0A0G2K1Q8, C0SPB4, E9PU17, E9PX95, E9Q876, F1MWM0, O35600, O52618, O95477, P08720, P0A9U1, P0A9U2, P0DXG8, P0DXU5, P0DXU7, P19844, P22040, P23703, P26050, P30750, P32010, P36879, P37624, P41233, P41234, P44785, P50332, P54592, P55476, P63355, P63356, P70970, P72335, P78363, P94374, P94440, Q05067, Q0I5E9, Q0TLD2, Q13ZJ1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 198 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	22.8×	3e-04
Unblocking of NMDA receptors, glutamate binding and activation	5	21.8×	3e-04
Negative regulation of NMDA receptor-mediated neuronal transmission	5	21.8×	3e-04
Long-term potentiation	5	19.0×	5e-04
Assembly and cell surface presentation of NMDA receptors	9	18.3×	3e-07
Neurexins and neuroligins	10	15.8×	3e-07
Protein-protein interactions at synapses	6	12.8×	5e-04
Formation of the dystrophin-glycoprotein complex (DGC)	5	12.3×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	32.3×	3e-10
receptor clustering	8	27.7×	2e-07
protein localization to synapse	6	25.5×	2e-05
regulation of postsynaptic membrane neurotransmitter receptor levels	7	19.3×	2e-05
protein-containing complex assembly	11	7.0×	9e-05
cell-cell adhesion	12	6.8×	5e-05
chemical synaptic transmission	10	4.3×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	37
Likely pathogenic	10
Uncertain significance	435
Likely benign	126
Benign	34

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1176588	NM_001606.5(ABCA2):c.4213C>T (p.Gln1405Ter)	Pathogenic
144296	GRCh38/hg38 9q34.11-34.3(chr9:130513207-138124532)x3	Pathogenic
148759	GRCh38/hg38 9q34.2-34.3(chr9:133504071-138159073)x3	Pathogenic
154569	GRCh38/hg38 9q34.13-34.3(chr9:132386553-138059695)x3	Pathogenic
154888	GRCh38/hg38 9q34.2-34.3(chr9:133918071-138159073)x3	Pathogenic
161082	GRCh38/hg38 9q34.3(chr9:136323974-138014606)x1	Pathogenic
2423367	NC_000009.11:g.(?139089171)(141016451_?)del	Pathogenic
2572524	NM_001606.5(ABCA2):c.1850del (p.Ser617fs)	Pathogenic
2580911	NM_001606.5(ABCA2):c.6630_6630+1del	Pathogenic
2684590	GRCh37/hg19 9q34.2-34.3(chr9:136988996-141020389)x3	Pathogenic
3238663	GRCh38/hg38 9q34.13-34.3(chr9:137590213-138052188)	Pathogenic
3238667	GRCh38/hg38 9q34.13-34.3(chr9:137552409-138059181)	Pathogenic
3238668	GRCh38/hg38 9q34.13-34.3(chr9:137552409-138052113)	Pathogenic
3238672	GRCh38/hg38 9q34.3(chr9:137529711-138129711)	Pathogenic
3238673	GRCh38/hg38 9q34.13-34.3(chr9:137552409-137879159)	Pathogenic
3238682	GRCh38/hg38 9q34.3(chr9:137569711-138129711)	Pathogenic
3238690	GRCh38/hg38 9q34.3(chr9:136817307-138133487)	Pathogenic
3238697	GRCh38/hg38 9q34.3(chr9:135008333-138199729)	Pathogenic
3238702	GRCh38/hg38 9q34.3(chr9:136869696-138172039)	Pathogenic
3238707	GRCh38/hg38 9q34.3(chr9:135203306-138100471)	Pathogenic
3238708	GRCh38/hg38 9q34.3(chr9:135791488-138262981)	Pathogenic
3238709	GRCh38/hg38 9q34.3(chr9:136684941-138124673)	Pathogenic
3390994	GRCh37/hg19 9q34.3(chr9:139694299-140792635)x1	Pathogenic
3391001	GRCh37/hg19 9q34.3(chr9:139559141-141093906)x1	Pathogenic
3391002	GRCh37/hg19 9q34.3(chr9:138557721-141138302)x1	Pathogenic
34625	GRCh38/hg38 9q34.3(chr9:136323974-138014606)x1	Pathogenic
3775582	NM_001606.5(ABCA2):c.672del (p.Met225fs)	Pathogenic
395356	GRCh37/hg19 9q33.3-34.3(chr9:128652785-141044751)x3	Pathogenic
4076010	GRCh37/hg19 9q34.3(chr9:139341867-140180723)x1	Pathogenic
442899	GRCh37/hg19 9q34.3(chr9:138209358-141020389)x1	Pathogenic

SpliceAI

7726 predictions. Top by Δscore:

Variant	Effect	Δscore
9:137008415:CCCG:C	donor_gain	1.0000
9:137008423:T:TA	donor_gain	1.0000
9:137008620:CAC:C	acceptor_gain	1.0000
9:137008711:AGTGC:A	donor_gain	1.0000
9:137008729:A:AC	donor_gain	1.0000
9:137008730:C:CC	donor_gain	1.0000
9:137008730:CA:C	donor_gain	1.0000
9:137008864:CGCTC:C	acceptor_gain	1.0000
9:137008866:CTC:C	acceptor_gain	1.0000
9:137008867:TC:T	acceptor_gain	1.0000
9:137008868:CC:C	acceptor_gain	1.0000
9:137008869:C:CC	acceptor_gain	1.0000
9:137008870:T:A	acceptor_loss	1.0000
9:137008947:GCACC:G	donor_loss	1.0000
9:137008949:A:AC	donor_gain	1.0000
9:137008950:C:CC	donor_gain	1.0000
9:137008950:C:CT	donor_loss	1.0000
9:137008964:T:TA	donor_gain	1.0000
9:137009052:ACCTG:A	acceptor_loss	1.0000
9:137009053:CCTGG:C	acceptor_loss	1.0000
9:137009054:C:CC	acceptor_gain	1.0000
9:137009368:A:AC	donor_gain	1.0000
9:137009369:C:CC	donor_gain	1.0000
9:137009369:CCGG:C	donor_gain	1.0000
9:137009459:CATG:C	acceptor_gain	1.0000
9:137009463:C:CC	acceptor_gain	1.0000
9:137009643:TCC:T	acceptor_loss	1.0000
9:137009645:C:CC	acceptor_gain	1.0000
9:137009645:CTGG:C	acceptor_loss	1.0000
9:137009763:ACTT:A	donor_loss	1.0000

AlphaMissense

15844 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:137008735:T:A	D2354V	1.000
9:137008735:T:G	D2354A	1.000
9:137008736:C:G	D2354H	1.000
9:137008753:A:T	V2348D	1.000
9:137009375:C:A	K2273N	1.000
9:137009375:C:G	K2273N	1.000
9:137009379:A:G	L2272P	1.000
9:137009395:C:G	G2267R	1.000
9:137009438:G:C	C2252W	1.000
9:137010675:C:G	R2039P	1.000
9:137011031:C:G	G1999R	1.000
9:137011236:A:G	L1957P	1.000
9:137011236:A:T	L1957H	1.000
9:137011245:C:T	G1954D	1.000
9:137011246:C:G	G1954R	1.000
9:137011248:A:G	L1953P	1.000
9:137011260:G:T	P1949H	1.000
9:137011284:A:G	L1941P	1.000
9:137011429:A:G	L1925P	1.000
9:137011432:A:G	L1924P	1.000
9:137011459:C:T	G1915D	1.000
9:137011460:C:G	G1915R	1.000
9:137011468:A:G	L1912P	1.000
9:137011470:A:C	N1911K	1.000
9:137011470:A:T	N1911K	1.000
9:137011483:A:G	L1907P	1.000
9:137011634:C:T	G1883E	1.000
9:137011635:C:A	G1883W	1.000
9:137011635:C:G	G1883R	1.000
9:137011635:C:T	G1883R	1.000

dbSNP variants (sampled 300 via entrez): RS1000008365 (9:137027747 G>A,C), RS1000096093 (9:137011610 G>A,T), RS1000251511 (9:137010461 A>G,T), RS1000430739 (9:137024957 C>A,G), RS1000532332 (9:137013637 C>A,T), RS1000690688 (9:137018123 C>G), RS1000796101 (9:137023598 G>A,T), RS1000817004 (9:137023638 A>C), RS1000940518 (9:137030164 A>G), RS1000978184 (9:137028459 G>C,T), RS1001244521 (9:137011644 G>A), RS1001291171 (9:137019611 G>A,C), RS1001355504 (9:137015724 G>A), RS1002014429 (9:137024523 G>A), RS1002071789 (9:137018702 C>G,T)

Disease associations

OMIM: gene MIM:600047 | disease phenotypes: MIM:614254, MIM:614959, MIM:615005, MIM:618808, MIM:614202, MIM:616276, MIM:616028, MIM:213300, MIM:610253

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder with poor growth and with or without seizures or ataxia	Strong	Autosomal recessive
schizophrenia	Limited	Unknown

Mondo (12): neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant (MONDO:0013655), developmental and epileptic encephalopathy, 14 (MONDO:0013989), autosomal dominant nocturnal frontal lobe epilepsy 5 (MONDO:0014002), intellectual developmental disorder with poor growth and with or without seizures or ataxia (MONDO:0032930), Rafiq syndrome (MONDO:0013624), neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome (MONDO:0014562), Adams-Oliver syndrome 5 (MONDO:0014459), Joubert syndrome (MONDO:0018772), Kleefstra syndrome 1 (MONDO:0027407), intellectual disability (MONDO:0001071), epilepsy (MONDO:0005027), schizophrenia (MONDO:0005090)

Orphanet (8): Epilepsy of infancy with migrating focal seizures (Orphanet:293181), Sleep-related hypermotor epilepsy (Orphanet:98784), Autosomal recessive non-syndromic intellectual disability (Orphanet:88616), Neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome (Orphanet:457185), Isolated Joubert syndrome (Orphanet:475), Adams-Oliver syndrome (Orphanet:974), Kleefstra syndrome (Orphanet:261494), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000519	Developmental cataract
HP:0000718	Aggressive behavior
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001256	Mild intellectual disability
HP:0001260	Dysarthria
HP:0001324	Muscle weakness
HP:0002066	Gait ataxia
HP:0002286	Fair hair
HP:0002311	Incoordination
HP:0003141	Increased LDL cholesterol concentration
HP:0011342	Mild global developmental delay
HP:0031936	Delayed ability to walk

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST009028_42	Adverse response to drug	5.000000e-07
GCST011379_6	Cutaneous mastocytosis (childhood)	1.000000e-18
GCST011380_1	Cutaneous mastocytosis (adult)	4.000000e-15
GCST011381_1	Cutaneous mastocytosis	2.000000e-30
GCST011382_3	Systemic mastocytosis	4.000000e-08
GCST011383_16	Mastocytosis	7.000000e-33
GCST90002407_84	White blood cell count	6.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009658	adverse effect

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C563043	Kleefstra Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2271862	ABCA2		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — ABCA subfamily

CTD chemical–gene interactions

40 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
beta-lapachone	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
aflatoxin B2	increases methylation	1
gypenoside	decreases expression	1
abrine	decreases expression	1
bisphenol S	affects cotreatment, increases methylation, decreases methylation	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Bortezomib	decreases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Amiodarone	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases response to substance, increases expression	1
Estradiol	decreases expression, affects cotreatment	1
Gallic Acid	decreases expression	1
Lead	affects expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Methotrexate	decreases response to substance, increases expression	1
Ribonucleotides	affects binding	1
Rifampin	increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Toluene	decreases expression, increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety