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): 919 total — 37 pathogenic, 12 likely-pathogenic (top 3% of genes corpus-wide)
• GTEx eGene: eQTL in 14 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 15
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.44 (moderately constrained)
• 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: 25 — 12 retained_intron, 7 protein_coding, 4 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000341511

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 5, TSL 2: 7, TSL 3: 2, TSL 5: 8

ENST00000341511, ENST00000371605, ENST00000398207, ENST00000425423, ENST00000431584, ENST00000437791, ENST00000459850, ENST00000463603, ENST00000464157, ENST00000464520, ENST00000464876, ENST00000466707, ENST00000467624, ENST00000470535, ENST00000476211, ENST00000479446, ENST00000487109, ENST00000488535, ENST00000490486, ENST00000492260, ENST00000494046, ENST00000614293, ENST00000970112, ENST00000970113, ENST00001138941

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.

Highest expression (Bgee): C1 segment of cervical spinal cord, spinal cord, hemisphere of cerebellum, frontal lobe, peripheral nervous system.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ABCA2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 14 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

15 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	sqtl	1.9e-19	-1.12	9:137017531:T:G
Whole Blood	eqtl	3.7e-16	+0.22	9:137032610:A:G
Colon Transverse	eqtl	5.8e-13	-0.33	9:136771753:A:C
Artery Aorta	eqtl	8.7e-09	+0.23	9:136992590:G:C
Artery Tibial	eqtl	1.3e-04	+0.12	9:137011907:G:A
Small Intestine Terminal Ileum	eqtl	1.4e-04	-0.41	9:136791837:A:G
Cells Cultured fibroblasts	eqtl	1.4e-04	-0.09	9:137001712:A:G
Skin Sun Exposed Lower leg	eqtl	1.4e-03	+0.14	9:137029055:C:CA
Skin Not Sun Exposed Suprapubic	eqtl	1.9e-03	+0.15	9:137029055:C:CA
Esophagus Mucosa	eqtl	3.8e-03	-0.15	9:137019767:C:T
Testis	eqtl	8.8e-03	-0.35	9:137006958:G:A
Esophagus Gastroesophageal Junction	eqtl	1.4e-02	+0.15	9:137030185:T:C
Nerve Tibial	eqtl	2.5e-02	-0.07	9:136358427:A:G
Spleen	eqtl	2.8e-02	-0.56	9:137689941:A:G
Adipose Visceral Omentum	eqtl	4.9e-02	-0.15	9:137645160:G:A

FANTOM5 promoters

showing 10 of 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

showing 100 of 287 tissues 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
apex of heart	UBERON:0002098	95.77	gold quality
neocortex	UBERON:0001950	95.75	gold quality
right lobe of thyroid gland	UBERON:0001119	95.61	gold quality
ventral tegmental area	UBERON:0002691	95.58	gold quality
central nervous system	UBERON:0001017	95.47	gold quality
forebrain	UBERON:0001890	95.44	gold quality
Brodmann (1909) area 10	UBERON:0013541	95.43	gold quality
brain	UBERON:0000955	95.35	gold quality
telencephalon	UBERON:0001893	95.27	gold quality
stromal cell of endometrium	CL:0002255	95.10	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	95.07	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.06	gold quality
cranial nerve II	UBERON:0000941	94.95	gold quality
left lobe of thyroid gland	UBERON:0001120	94.91	gold quality
superior vestibular nucleus	UBERON:0007227	94.55	gold quality
cerebral cortex	UBERON:0000956	94.52	gold quality
subthalamic nucleus	UBERON:0001906	94.50	gold quality
postcentral gyrus	UBERON:0002581	94.45	gold quality
midbrain	UBERON:0001891	94.31	gold quality
parietal lobe	UBERON:0001872	94.19	gold quality
substantia nigra	UBERON:0002038	94.14	gold quality
temporal lobe	UBERON:0001871	93.76	gold quality
thyroid gland	UBERON:0002046	93.74	gold quality
CA1 field of hippocampus	UBERON:0003881	93.41	gold quality
cortical plate	UBERON:0005343	93.39	gold quality
right uterine tube	UBERON:0001302	93.12	gold quality
dorsal plus ventral thalamus	UBERON:0001897	93.09	gold quality
paraflocculus	UBERON:0005351	92.87	gold quality
body of stomach	UBERON:0001161	92.67	gold quality
right lobe of liver	UBERON:0001114	92.27	gold quality
frontal pole	UBERON:0002795	91.93	gold quality
superior frontal gyrus	UBERON:0002661	91.23	gold quality
ventricular zone	UBERON:0003053	91.05	gold quality
descending thoracic aorta	UBERON:0002345	90.97	gold quality
left coronary artery	UBERON:0001626	90.89	gold quality
metanephros cortex	UBERON:0010533	90.82	gold quality
spleen	UBERON:0002106	90.75	gold quality
right atrium auricular region	UBERON:0006631	90.62	gold quality
ascending aorta	UBERON:0001496	90.42	gold quality
thoracic aorta	UBERON:0001515	90.32	gold quality
transverse colon	UBERON:0001157	90.21	gold quality
pons	UBERON:0000988	90.02	gold quality
mucosa of transverse colon	UBERON:0004991	89.81	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.68	gold quality
coronary artery	UBERON:0001621	89.64	gold quality
right coronary artery	UBERON:0001625	89.55	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.48	gold quality
right adrenal gland cortex	UBERON:0035827	89.37	gold quality
left adrenal gland cortex	UBERON:0035825	89.32	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.24	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.12	gold quality
heart left ventricle	UBERON:0002084	88.99	gold quality
lateral globus pallidus	UBERON:0002476	88.92	gold quality
lower esophagus mucosa	UBERON:0035834	88.89	gold quality
substantia nigra pars reticulata	UBERON:0001966	88.86	gold quality
ganglionic eminence	UBERON:0004023	88.84	gold quality
right adrenal gland	UBERON:0001233	88.81	gold quality
stomach	UBERON:0000945	88.75	gold quality
left adrenal gland	UBERON:0001234	88.66	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.56	gold quality
lower esophagus	UBERON:0013473	88.54	gold quality
endocervix	UBERON:0000458	88.33	gold quality
cardiac atrium	UBERON:0002081	88.32	gold quality
gall bladder	UBERON:0002110	88.32	gold quality
cardiac ventricle	UBERON:0002082	88.27	gold quality
occipital lobe	UBERON:0002021	88.23	gold quality
aorta	UBERON:0000947	87.97	gold quality
Brodmann (1909) area 46	UBERON:0006483	87.71	gold quality
skin of abdomen	UBERON:0001416	87.69	gold quality
omental fat pad	UBERON:0010414	87.67	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

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Corpus callosum	tissue	448.4
Nucleus accumbens	tissue	319.1
Spinal cord	tissue	267.8
Locus coeruleus	tissue	251.2
Hippocampus	tissue	249.7	high
Medulla oblongata	tissue	243.5
Midbrain	tissue	226.5
Substantia nigra	tissue	222.8
Thalamus	tissue	187.9
Superior colliculi	tissue	185.3
Pons	tissue	169.2
Putamen	tissue	160.2
Ventral forebrain	tissue	158.9
Postcentral gyrus	tissue	152.3
Periaqueductal gray	tissue	130.9
Hypothalamus	tissue	129.8
Hippocampal formation	tissue	119.6
Septum	tissue	109.1
Cerebral cortex	tissue	98.0	medium
Somatosensory cortex	tissue	98.0
Retrosplenial cortex	tissue	91.5
Occipital cortex	tissue	87.2
Amygdala	tissue	86.1
Motor cortex	tissue	85.9
Insular cortex	tissue	84.7
Choroid plexus	tissue	75.1
Cerebellum	tissue	75.0	medium
Retrosplenial and cingulate cortex	tissue	74.2
Prefrontal cortex	tissue	74.0
Basal ganglia	tissue	72.8	high
Temporal cortex	tissue	67.5
Entorhinal cortex	tissue	66.0
Caudate putamen	tissue	64.3
Olfactory bulb	tissue	53.6
Frontal cortex	tissue	43.4
Pituitary gland	tissue	19.9
Parathyroid gland	tissue	12.5	medium
Thyroid gland	tissue	9.4	medium
Pancreas	tissue	8.8	medium
Adipose tissue	tissue	8.5	not detected
Spleen	tissue	8.1	low
Salivary gland	tissue	7.7	medium
Heart muscle	tissue	7.2	low
Skeletal muscle	tissue	6.3	medium
Stomach 1	tissue	6.0	medium
Fallopian tube	tissue	5.9	medium
Adrenal gland	tissue	5.7	medium
Gallbladder	tissue	5.5	medium
Bone marrow	tissue	5.5	medium
Skin 1	tissue	5.3	medium
Prostate	tissue	4.8	medium
Vagina	tissue	4.5	medium
Seminal vesicle	tissue	4.4	low
Epididymis	tissue	4.3	medium
Lymph node	tissue	4.2	medium
Colon	tissue	4.2	medium
Kidney	tissue	4.1	medium
Small intestine	tissue	3.9	medium
Lung	tissue	3.8	medium
Appendix	tissue	3.5	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Parieto-temporal junction (white matter) (1211.4), Temporal white matter (1053.8), Corpus callosum, splenium (white matter) (895.8), Corpus callosum, genu (white matter) (797.5), Cerebellar white matter (746.1).

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

Targeting ABCA2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 44 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.436, missense Z 3.74 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000341511 splits into 12 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
9:137,007,932–137,009,042	212 / 214.4	0.99	no
9:137,009,043–137,012,843	602 / 897.4	0.67	no
9:137,012,844–137,013,473	192 / 207.2	0.93	no
9:137,013,474–137,013,989	75 / 118.3	0.63	no
9:137,013,990–137,015,443	297 / 286.5	1.04	no
9:137,015,444–137,016,358	180 / 307.3	0.59	no
9:137,016,359–137,016,968	133 / 150.8	0.88	no
9:137,016,969–137,018,197	188 / 343.4	0.55	no
9:137,018,198–137,019,213	187 / 205.9	0.91	no
9:137,019,214–137,020,753	92 / 146.7	0.63	no
9:137,020,754–137,022,777	403 / 375.9	1.07	no
9:137,022,778–137,028,140	101 / 152.3	0.66	no

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:99606) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 20 distinct phenotype terms.

Mouse phenotype (MP)	Records
tremors	2
decreased body weight	2
abnormal coat/ hair morphology	1
hyperactivity	1
increased exploration in new environment	1
increased startle reflex	1
abnormal motor coordination/balance	1
impaired balance	1
abnormal lipid level	1
increased circulating phosphate level	1
reduced female fertility	1
abnormal emotion/affect behavior	1
increased vertical activity	1
increased fear-related response	1
enhanced coordination	1
abnormal myelin sheath morphology	1
increased susceptibility to induced morbidity/mortality	1
decreased grip strength	1
increased bone mineral content	1
increased locomotor activity	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Escherichia coli K-12	P0A9U1	100.0%	Diamond
Shigella flexneri	P0A9U2	100.0%	Diamond
Mycobacterium tuberculosis CDC1551	P9WQL8	100.0%	Diamond
Mycobacterium tuberculosis H37Rv	P9WQL9	100.0%	Diamond
Burkholderia pseudomallei 1710b	Q3JSQ0	100.0%	Diamond
Burkholderia mallei ATCC 23344	Q62K72	100.0%	Diamond
Oryza sativa Indica Group	A2WSH0	99.9%	Diamond
Oryza sativa Japonica Group	Q0JLC5	99.9%	Diamond
Petunia axillaris	H6WS93	99.7%	Diamond
Petunia x hybrida	H6WS94	99.7%	Diamond
Rhizobium leguminosarum bv. viciae	P08720	99.7%	Diamond
Rhizobium johnstonii 3841	Q1M7W6	99.7%	Diamond
Burkholderia pseudomallei K96243	Q63TX3	99.7%	Diamond
Streptomyces coeruleorubidus	P0DXG8	99.4%	Diamond
Streptomyces peucetius	P32010	99.4%	Diamond
Bradyrhizobium diazoefficiens USDA 110	P26050	97.4%	Diamond
Bradyrhizobium sp. SNU001	Q9Z3I3	97.4%	Diamond
Burkholderia orbicola AU 1054	Q1BWI2	95.7%	Diamond
Burkholderia lata	Q39GT7	95.7%	Diamond
Burkholderia thailandensis E264	Q2SVP3	95.1%	Diamond
Arabidopsis thaliana	Q7PC81	94.3%	Diamond
Sinorhizobium meliloti 1021	O52618	91.9%	Diamond
Sinorhizobium meliloti	Q8GNH6	91.9%	Diamond
Bos taurus	F1MWM0	89.4%	Diamond
Cupriavidus metallidurans CH34	Q1LKJ2	87.8%	Diamond
Cupriavidus pinatubonensis JMP134	Q46YX6	87.8%	Diamond
Paraburkholderia xenovorans LB400	Q13ZJ1	83.6%	Diamond
Staphylococcus saprophyticus subsp. saprophyticus ATCC 15305 = NCTC 7292	Q49VI3	83.3%	Diamond
Nicotiana tabacum	Q76CU2	83.0%	Diamond
Nicotiana plumbaginifolia	Q949G3	83.0%	Diamond
Mesorhizobium japonicum MAFF 303099	P23703	82.5%	Diamond
Rhizobium sp. N33	P72335	82.5%	Diamond
Rhizobium etli CFN 42	Q8KLG1	80.0%	Diamond
Sinorhizobium fredii NGR234	P55476	77.5%	Diamond
Ralstonia pseudosolanacearum GMI1000	Q8XXY9	74.7%	Diamond
Neorhizobium galegae	P50332	74.6%	Diamond
Nostoc sp. PCC 7120 = FACHB-418	Q05067	63.4%	Diamond
Synechocystis sp. PCC 6803 substr. Kazusa	P22040	63.2%	Diamond
Dictyostelium discoideum	Q55BC0	57.7%	Diamond
Methanocaldococcus jannaschii DSM 2661	Q58429	47.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
FUT7	protein-coding	2529
PAXX	protein-coding	286257
LINC02908	ncRNA	401563
NPDC1	protein-coding	56654
CLIC3	protein-coding	9022
LCNL1	protein-coding	401562
PTGDS	protein-coding	5730
ENTPD2	protein-coding	954
SAPCD2	protein-coding	89958

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): A0A087WXK5, E9PGB2, Q9BZC7, 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, PF26955

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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Transporters, Primary Active Transporters, Predicted membrane proteins, Predicted intracellular proteins, Plasma proteins, Disease related genes, Potential drug targets, Human disease related genes, Mental and behavioural disorders

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles

Antibody reliability (HPA): IH approved · IF supported

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)

Position	Role
1024–1031	ATP
2087–2094	ATP

Post-translational modifications (5)

Type	Positions
N5-methylglutamine	271
Phosphoserine	1238, 1327, 1331
Phosphothreonine	2412

Glycosylation sites (25)

Type	Positions
N-linked (glcnac…) asparagine	14, 89, 168, 173, 305, 368, 379, 420, 432, 476, 484, 494, 530, 544, 590, 600, 628, 1408, 1496, 1549, 1557, 1612, 1677, 1775, 2054

Mutagenesis-validated functional residues (1)

Position	Phenotype
271	abolishes methylation by n6amt1.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

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

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 (34): 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), lipid translocation (GO:0034204), regulation of protein metabolic process (GO:0051246), positive regulation of protein metabolic process (GO:0051247)

GO Molecular Function (10): 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), protein binding (GO:0005515), 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

2 top-level categories:

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

GO top-level categories

showing 60 of 76 GO namespaces:

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
phospholipid biosynthetic process	1
negative regulation of lipid biosynthetic process	1
regulation of phospholipid biosynthetic process	1
negative regulation of phospholipid metabolic process	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular carrier activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
ribonucleoside triphosphate phosphatase activity	1
primary active transmembrane transporter activity	1
ATP hydrolysis activity	1
endopeptidase activity	1
peptidase regulator activity	1
sphingolipid floppase activity	1
ceramide translocation	1
ATPase-coupled transmembrane transporter activity	1
binding	1
ATPase-coupled intramembrane lipid carrier activity	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 27 of 54 annotations. The rest are phylogenetic / computational / electronic (IEA).

27 experimentally-supported GO terms:

GO term	NS	Evidence
ceramide translocation	BP	direct assay
cholesterol homeostasis	BP	expression pattern
intracellular sphingolipid homeostasis	BP	direct assay
negative regulation of cholesterol efflux	BP	direct assay
negative regulation of intracellular cholesterol transport	BP	direct assay
negative regulation of phospholipid biosynthetic process	BP	direct assay
negative regulation of receptor-mediated endocytosis involved in cholesterol transport	BP	direct assay
negative regulation of sphingolipid biosynthetic process	BP	direct assay
positive regulation of amyloid precursor protein biosynthetic process	BP	direct assay
positive regulation of amyloid precursor protein catabolic process	BP	mutant phenotype
positive regulation of amyloid-beta formation	BP	mutant phenotype
positive regulation of low-density lipoprotein particle receptor catabolic process	BP	direct assay
regulation of intracellular cholesterol transport	BP	mutant phenotype
regulation of post-translational protein modification	BP	mutant phenotype
regulation of steroid metabolic process	BP	direct assay
response to cholesterol	BP	expression pattern
response to steroid hormone	BP	expression pattern
sphingosine biosynthetic process	BP	direct assay
endosome	CC	direct assay
endosome membrane	CC	direct assay
lysosomal membrane	CC	direct assay
lysosome	CC	direct assay
membrane	CC	direct assay
plasma membrane	CC	direct assay
ATP binding	MF	direct assay
ceramide floppase activity	MF	direct assay
endopeptidase regulator activity	MF	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 794 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABCA2	ELP6	Q0PNE2	737
ABCA2	HMGCS1	Q01581	609
ABCA2	CYP46A1	Q9Y6A2	602
ABCA2	ABCC3	O15438	586
ABCA2	BLMH	Q13867	535
ABCA2	ABCD4	O14678	483
ABCA2	ABCF1	Q8NE71	472
ABCA2	APP	P05067	464
ABCA2	APBB2	Q92870	459
ABCA2	GSTO1	P78417	452
ABCA2	HSD11B1	P28845	449
ABCA2	GAB2	Q9UQC2	442
ABCA2	SLCO1A2	P46721	440
ABCA2	UBQLN1	Q9UMX0	432
ABCA2	GSTO2	Q9H4Y5	429

IntAct

Human interaction partners of ABCA2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 87 partners by confidence:

Partner	Interaction type	MIscore	Records
PATJ	direct interaction	0.440	9
GRIP1	direct interaction	0.440	5
GRIP2	direct interaction	0.440	5
MAGI2	direct interaction	0.440	4
FRMPD2	direct interaction	0.440	3
LNX1	direct interaction	0.440	3
MPDZ	direct interaction	0.440	3
NHERF4	direct interaction	0.440	3
PDZK1	direct interaction	0.440	3
SCRIB	direct interaction	0.440	3
WHRN	direct interaction	0.440	3
APBA1	direct interaction	0.440	2
APBA2	direct interaction	0.440	2
DLG3	direct interaction	0.440	2
GRID2IP	direct interaction	0.440	2
IL16	direct interaction	0.440	2
MAGI1	direct interaction	0.440	2
TJP1	direct interaction	0.440	2
AHNAK	direct interaction	0.440	1
APBA3	direct interaction	0.440	1
ARHGAP21	direct interaction	0.440	1
ARHGEF11	direct interaction	0.440	1
ARHGEF12	direct interaction	0.440	1
CARD11	direct interaction	0.440	1
CASK	direct interaction	0.440	1
DLG1	direct interaction	0.440	1
DLG2	direct interaction	0.440	1
DLG4	direct interaction	0.440	1
DLG5	direct interaction	0.440	1
DVL3	direct interaction	0.440	1

BioGRID (126 interactions; top human partners by supporting records): PON2 (Affinity Capture-MS; 3 records), PTCH1 (Affinity Capture-MS; 3 records), FBXO6 (Affinity Capture-MS; 2 records), HTR3A (Affinity Capture-MS; 2 records), LMAN2L (Affinity Capture-MS; 2 records), ZNRF4 (Affinity Capture-MS; 2 records), ABCA1 (Co-fractionation), ABCA6 (Affinity Capture-MS), ABCB9 (Affinity Capture-MS), ABCD4 (Affinity Capture-MS), ABI2 (Co-fractionation), ADCY3 (Affinity Capture-MS), AGR2 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), ATP5A1 (Affinity Capture-MS)

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 87 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	48.4×	3e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	46.1×	3e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	46.1×	3e-06
Long-term potentiation	5	40.3×	5e-06
Assembly and cell surface presentation of NMDA receptors	9	38.7×	1e-10
Neurexins and neuroligins	10	33.4×	7e-11
Protein-protein interactions at synapses	6	27.0×	3e-06
RHOB GTPase cycle	5	13.1×	9e-04

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	69.2×	6e-14
protein localization to synapse	6	54.7×	1e-07
receptor clustering	7	52.0×	1e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	7	41.3×	6e-08
cell-cell adhesion	10	12.1×	1e-06
protein-containing complex assembly	8	10.8×	5e-05
regulation of small GTPase mediated signal transduction	5	8.6×	7e-03
chemical synaptic transmission	9	8.3×	8e-05

Disease & clinical

Genetic variants

Variant evidence for ABCA2: 919 ClinVar records (49 pathogenic / likely pathogenic); 7 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	37
Likely pathogenic	12
Uncertain significance	464
Likely benign	298
Benign	24

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 49 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
2580911	NM_001606.5(ABCA2):c.6630_6630+1del	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1527942	NM_001606.5(ABCA2):c.4108C>T (p.Gln1370Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
637957	NM_001606.5(ABCA2):c.4903del (p.Val1635fs)	Pathogenic	criteria provided, single submitter	2
828057	NM_001606.5(ABCA2):c.937C>T (p.Gln313Ter)	Pathogenic	criteria provided, single submitter	2
828058	NM_001606.5(ABCA2):c.650dup (p.Gly218fs)	Pathogenic	criteria provided, single submitter	2
1176588	NM_001606.5(ABCA2):c.4213C>T (p.Gln1405Ter)	Pathogenic	criteria provided, single submitter	1
2572524	NM_001606.5(ABCA2):c.1850del (p.Ser617fs)	Pathogenic	criteria provided, single submitter	1
3775582	NM_001606.5(ABCA2):c.672del (p.Met225fs)	Pathogenic	criteria provided, single submitter	1
1315390	NM_001606.5(ABCA2):c.1703G>A (p.Trp568Ter)	Likely pathogenic	criteria provided, single submitter	1
2435952	NM_001606.5(ABCA2):c.846del (p.Leu283fs)	Likely pathogenic	criteria provided, single submitter	1
2576968	NM_001606.5(ABCA2):c.5923+1G>A	Likely pathogenic	criteria provided, single submitter	1
3657213	NM_001606.5(ABCA2):c.5924-2A>C	Likely pathogenic	criteria provided, single submitter	1
3906178	NM_001606.5(ABCA2):c.4015_4016insA (p.Ser1339fs)	Likely pathogenic	criteria provided, single submitter	1
4845700	NM_001606.5(ABCA2):c.4124C>A (p.Ser1375Ter)	Likely pathogenic	criteria provided, single submitter	1
4857663	NM_001606.5(ABCA2):c.6382C>T (p.Gln2128Ter)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore ABCA2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 29 predictions of 4,089):

Position(s)	Effect	Δscore	Sites
9:137008869–137008870	acceptor_loss	1.0000	4
9:137008950	donor_loss	1.0000
9:137009054–137009055	acceptor_loss	1.0000	2
9:137009645–137009646	acceptor_loss	1.0000	5
9:137009767–137009768	donor_loss	1.0000	4
9:137009904	acceptor_loss	1.0000	2
9:137009909–137009910	acceptor_gain	1.0000	2
9:137009981–137009982	donor_loss	1.0000	5
9:137010619	donor_loss	1.0000	3
9:137010739	acceptor_gain	1.0000

AlphaMissense

6,100 missense substitutions predicted likely pathogenic (of 15,844 scored), across 1,282 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M1958	9	0.954	0.996
M1127	9	0.953	0.993
M1995	9	0.947	0.998
M1181	9	0.945	0.997
M2245	9	0.939	0.996
M1890	9	0.935	0.997
M2216	9	0.934	0.993
M1472	9	0.932	0.998
M738	9	0.917	0.994
M829	9	0.913	0.998
M1802	9	0.908	0.999
M2099	9	0.905	0.996
M2258	9	0.864	0.993
M1059	9	0.825	0.955
D2354	8	0.999	1.000
D1147	8	0.998	1.000
D1843	8	0.997	0.999
D1154	8	0.995	0.999
D902	8	0.994	0.999
F1804	8	0.994	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.25e-06
Breast Invasive Carcinoma (validation)	favorable	0.000338

Disease associations

OMIM: gene MIM:600047 | disease phenotypes: MIM:618808, MIM:614202

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
intellectual developmental disorder with poor growth and with or without seizures or ataxia	Strong	Autosomal recessive	4
schizophrenia	Limited	Unknown

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (9 panels, 4 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

9 panels:

Panel	Rating
DDG2P	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Ataxia and cerebellar anomalies - childhood onset	amber
Early onset or syndromic epilepsy	amber
Hereditary ataxia and cerebellar anomalies, childhood onset	amber
Paediatric disorders	amber
Unexplained death in infancy and sudden unexplained death in childhood	amber

Mondo (3): intellectual developmental disorder with poor growth and with or without seizures or ataxia (MONDO:0032930), Rafiq syndrome (MONDO:0013624), schizophrenia (MONDO:0005090)

Orphanet (1): Autosomal recessive non-syndromic intellectual disability (Orphanet:88616)

HPO phenotypes

15 phenotypes (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	Elevated circulating LDL-C concentration
HP:0011342	Mild global developmental delay
HP:0031936	Delayed ability to walk

GWAS associations

7 associations:

Study	Trait	p-value
GCST011383_17	Mastocytosis	7e-33
GCST011381_10	Cutaneous mastocytosis	2e-30
GCST011379_6	Cutaneous mastocytosis (childhood)	1e-18
GCST011380_1	Cutaneous mastocytosis (adult)	4e-15
GCST90002407_202	White blood cell count	6e-9
GCST011382_14	Systemic mastocytosis	4e-8
GCST009028_6	Adverse response to drug	5e-7

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0009658	adverse effect

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs2271862	XELOX	Toxicity	Genotype AA is associated with decreased likelihood of Neutropenia when treated with XELOX in people with Colorectal Neoplasms and Neoplasm Metastasis as compared to genotypes AG + GG.	PMID:37653272

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — ABCA subfamily

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects cotreatment, decreases expression, increases abundance	2
Arsenic	affects cotreatment, decreases expression, increases abundance, affects methylation	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
beta-lapachone	increases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	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	affects cotreatment, increases methylation	1
Amiodarone	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Diazinon	increases methylation	1
Dieldrin	increases expression	1
Doxorubicin	decreases response to substance, increases expression	1
Estradiol	affects cotreatment, decreases expression	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

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 321 trials:

NCT	Phase	Status	Title
NCT00000374	Phase 4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	Phase 4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	Phase 4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	Phase 4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	Phase 4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	Phase 4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	Phase 4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	Phase 4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	Phase 4	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	Phase 4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	Phase 4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	Phase 4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	Phase 4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	Phase 4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	Phase 4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	Phase 4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	Phase 4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	Phase 4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	Phase 4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	Phase 4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	Phase 4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	Phase 4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	Phase 4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	Phase 4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	Phase 4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	Phase 4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	Phase 4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	Phase 4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	Phase 4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	Phase 4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	Phase 4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	Phase 4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	Phase 4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	Phase 4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	Phase 4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	Phase 4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	Phase 4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	Phase 4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	Phase 4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	Phase 4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety
NCT00177580	Phase 4	COMPLETED	Improving Symptoms of Schizophrenia and Schizoaffective Disorder by Supplementing Medications With Pravastatin
NCT00182442	Phase 4	COMPLETED	Cognition, Functioning and Quality of Life
NCT00182494	Phase 4	UNKNOWN	Diabetes Prevention Program in Schizophrenia [DPPS]
NCT00183625	Phase 4	COMPLETED	Supported Employment and Skills Training in Conjunction With Pharmacotherapy in Schizophrenia Patients
NCT00186771	Phase 4	UNKNOWN	Magnetic Stimulation as a Treatment for Auditory Hallucinations in Schizophrenia
NCT00190749	Phase 4	COMPLETED	Safety Study of Olanzapine and a Comparator in Patients With Schizophrenia and Schizoaffective Disorder
NCT00191555	Phase 4	COMPLETED	Efficacy Study of Switching Stabilized Schizophrenic Patients From Conventional to Atypical Antipsychotic Treatment
NCT00194025	Phase 4	COMPLETED	Valproate in Late Life Schizophrenia
NCT00199940	Phase 4	COMPLETED	Safety And Efficacy Study Of Ziprasidone In Pediatric Psychotic Illness
NCT00202306	Phase 4	COMPLETED	Indicated Prevention of Psychotic Disorders With Low-dose Lithium
NCT00203788	Phase 4	COMPLETED	Improving Work Outcome in People With Recent-onset Schizophrenia
NCT00204061	Phase 4	COMPLETED	Early Pharmacological and Psychological Intervention for Late Prodromal States of Psychosis
NCT00205660	Phase 4	COMPLETED	Changes in Adiposity, Metabolic Measures From Atypicals to Aripiprazole
NCT00206102	Phase 4	COMPLETED	A Study of the Cataractogenic Potential of Seroquel and Risperdal in the Treatment of Participants With Schizophrenia or Schizoaffective Disorder
NCT00208143	Phase 4	COMPLETED	Seroquel Therapy for Substance Use Disorders Comorbid With Schizophrenia
NCT00208169	Phase 4	COMPLETED	Abilify Therapy for Reducing Comorbid Substance Abuse
NCT00214578	Phase 4	COMPLETED	Seroquel on Glucose Metabolism
NCT00215579	Phase 4	COMPLETED	Determining the Effects of Risperdal Consta in Patients With Psychotic Disorders and Incomplete Adherence
NCT00216528	Phase 4	COMPLETED	A Study to Evaluate Symptomatic Remission in Schizophrenia With Long Acting Risperidone Microspheres
NCT00216632	Phase 4	COMPLETED	A Study of Treatment Success in Changing From Olanzapine to Long-acting Injectable Risperidone (RISPERDAL® CONSTA™)